Abilify

Name: Abilify

Cautions for Abilify

Contraindications

  • Known hypersensitivity to aripiprazole; hypersensitivity reactions have ranged from pruritus/urticaria to anaphylaxis.1 118 119 (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Warnings

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Increased risk of death with use of either conventional (first-generation) or atypical (second-generation) antipsychotics in geriatric patients with dementia-related psychosis.1 28 73 113 114 118 119

Antipsychotic agents, including aripiprazole, are not approved for the treatment of dementia-related psychosis.1 73 113 118 119 (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning, see Cerebrovascular Events in Geriatric Patients with Dementia-related Psychosis under Cautions, and see Dysphagia under Cautions.)

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.1 76 77 78 79 (See Boxed Warning and also see Pediatric Use under Cautions.) However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.1 76 77 78

Appropriately monitor and closely observe patients receiving aripiprazole for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.1 76 77 78

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.1 77 78 Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.1 76 77 78

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.1 77

Sensitivity Reactions

Allergic and sensitivity reactions (e.g., anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, photosensitivity, rash, oropharyngeal spasm) reported in aripiprazole-treated patients.1 118 119 (See Contraindications under Cautions.)

Other Warnings and Precautions

Cerebrovascular Events in Geriatric Patients with Dementia-related Psychosis

Increased incidence of adverse cerebrovascular events (cerebrovascular accidents and TIAs), including fatalities, observed in geriatric patients with dementia-related psychosis treated with aripiprazole in several placebo-controlled studies.1 118 Aripiprazole is not approved for the treatment of patients with dementia-related psychosis.1 118 119 (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Impulse Control/Compulsive Behaviors

Serious impulse-control and compulsive behaviors, particularly pathological gambling, reported in adult and pediatric patients treated with aripiprazole.123 132 134 135 136 137 138 In May 2016, FDA reported that 184 cases of impulse-control problems associated with aripiprazole therapy had been identified since November 2002; 89% of the cases involved pathological gambling.123 Other impulse-control and compulsive behaviors (e.g., compulsive or binge eating, compulsive spending or shopping, compulsive sexual behaviors) reported less frequently.123 136 138 Most of the patients had no history of compulsive behaviors and experienced the uncontrollable urges only after beginning aripiprazole treatment.123 137 These urges stopped within days to weeks following aripiprazole dosage reduction or discontinuance; recurrence of compulsive behaviors following rechallenge reported.123 134 136 137 138

Advise patients and caregivers of the risk of uncontrollable urges with aripiprazole and specifically ask patients whether they have developed any new or increased urges while receiving the drug.123 If an aripiprazole-treated patient develops new or increased impulsive or compulsive behaviors, consider reducing the dosage or discontinuing the drug.123 137 (See Advice to Patients.)

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability, reported with antipsychotic agents, including some rare cases in patients treated with aripiprazole.1 99 100 101 118 119

Immediately discontinue therapy and initiate supportive and symptomatic treatment if NMS occurs.1 118 119 Careful monitoring recommended if therapy is reinstituted following recovery; the risk that NMS can recur must be considered.1 118 119

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary dyskinetic movements, reported with use of antipsychotic agents, including aripiprazole.1 96 97 118 119

Reserve long-term antipsychotic treatment for patients with chronic illness known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate.1 118 119 In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.1 118 119

APA recommends assessing patients receiving atypical antipsychotic agents for abnormal involuntary movements every 12 months; for patients at increased risk for tardive dyskinesia, assess every 6 months.28 Consider discontinuance of aripiprazole if signs and symptoms of tardive dyskinesia appear.1 118 119 However, some patients may require treatment despite the presence of the syndrome.1 118 119

Metabolic Changes

Atypical antipsychotic agents are associated with metabolic changes, including hyperglycemia and diabetes mellitus, dyslipidemia, and weight gain.1 118 119 While all atypical antipsychotics produce some metabolic changes, each drug has its own specific risk profile.1 118 119 (See Hyperglycemia and Diabetes Mellitus, see Dyslipidemia, and also see Weight Gain under Cautions.)

Hyperglycemia and Diabetes Mellitus

Hyperglycemia, sometimes severe and associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents.1 In short- and longer-term clinical studies in adult and pediatric patients, clinically important differences between oral aripiprazole and placebo in mean change from baseline to end point in serum glucose concentrations not observed.1

Periodically monitor patients with an established diagnosis of diabetes mellitus for worsening of glucose control and perform fasting glucose testing at baseline and periodically in patients with risk factors for diabetes (e.g., obesity, family history of diabetes).1 If manifestations of hyperglycemia occur in any aripiprazole-treated patient, perform fasting blood glucose testing.1 (See Advice to Patients.)

Some patients who developed hyperglycemia while receiving an atypical antipsychotic have required continuance of antidiabetic treatment despite discontinuance of the atypical antipsychotic; in other patients, hyperglycemia resolved with discontinuance of the antipsychotic.1

Dyslipidemia

Undesirable changes in lipid parameters observed in patients treated with some atypical antipsychotics.1 However, aripiprazole generally does not appear to adversely affect the lipid profile.1

Weight Gain

Weight gain observed with atypical antipsychotic therapy.1 Monitoring of weight recommended during aripiprazole therapy.1 (See Hyperglycemia and Diabetes Mellitus under Cautions.)

Orthostatic Hypotension

Risk of orthostatic hypotension associated with adverse effects, including postural dizziness, syncope, and tachycardia, perhaps because of aripiprazole's α1-adrenergic blocking activity.1 118 119 Risk generally appears greatest during initiation of therapy and dosage titration.119

Use with caution in patients with known cardiovascular or cerebrovascular disease and/or conditions that would predispose them to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy) and in antipsychotic-naive patients.1 119 In such patients who are receiving extended-release IM aripiprazole lauroxil therapy, consider a lower initial dosage and monitoring of orthostatic vital signs.119

If parenteral benzodiazepine therapy is necessary in patients receiving short-acting IM aripiprazole, monitor patients for possible excessive sedation and orthostatic hypotension.1 (See Specific Drugs under Interactions.)

Leukopenia, Neutropenia, and Agranulocytosis

Leukopenia and neutropenia temporally related to antipsychotic agents, including aripiprazole, reported during clinical trial and/or postmarketing experience.1 102 103 118 119 Agranulocytosis also reported.1 118 119

Possible risk factors for leukopenia and neutropenia include preexisting low WBC count and a history of drug-induced leukopenia or neutropenia.1 102 103 118 119 Monitor CBC frequently during the first few months of therapy in patients with such risk factors.1 118 119 Discontinue aripiprazole at the first sign of a decline in WBC count in the absence of other causative factors.1 118 119

Carefully monitor patients with neutropenia for signs and symptoms of infection (e.g., fever) and treat promptly if they occur.1 118 119 Discontinue aripiprazole if severe neutropenia (ANC <1000/mm3) occurs; monitor WBC until recovery occurs.1 118 119

Seizures

Seizures/convulsions reported in 0.1% of adult and pediatric patients (6–18 years of age) treated with oral aripiprazole and in 0.2% of adults treated with short-acting IM aripiprazole.1

Use with caution in patients with a history of seizures or with conditions known to lower the seizure threshold; such conditions may be more prevalent in patients ≥65 years of age.1 118 119

Cognitive and Motor Impairment

Judgment, thinking, or motor skills may be impaired.1 118 119

Somnolence (including sedation) reported in 11 and 9% of adults treated with oral or short-acting parenteral aripiprazole, respectively, compared with 6% of those receiving placebo in short-term clinical trials.1 Somnolence (including sedation) reported in 24% of pediatric patients (6–17 years of age) receiving aripiprazole compared with 6% of those receiving placebo.1 (See Advice to Patients.)

Body Temperature Regulation

Antipsychotic agents may disrupt ability to reduce core body temperature.1 118 119

Use appropriate caution in patients exposed to conditions that may contribute to an elevation in core body temperature (e.g., dehydration, extreme heat, strenuous exercise, concomitant use of anticholinergic agents).1 118 119

Suicide

Attendant risk with psychotic illnesses, bipolar disorder, and major depressive disorder; closely supervise high-risk patients.1 Prescribe in the smallest quantity consistent with good patient management to reduce the risk of overdosage.1

Dysphagia

Esophageal dysmotility and aspiration associated with the use of antipsychotic agents, including aripiprazole.1 118 119

Aspiration pneumonia is a common cause of morbidity and mortality in geriatric patients, particularly in those with advanced Alzheimer’s dementia.1 (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.) Use with caution in patients at risk for aspiration pneumonia.1 118 119

Phenylketonuria

Each 10- or 15-mg Abilify Discmelt orally disintegrating tablet contains aspartame (NutraSweet), which is metabolized in the GI tract to provide about 1.12 or 1.68 mg of phenylalanine, respectively.1 80 81 82 83 84

Specific Populations

Pregnancy

Category C.1

Risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester; monitor neonates exhibiting such symptoms.1 106 107 108 111 118 119 Symptoms varied in severity; some neonates recovered within hours to days without specific treatment, while others have required intensive care unit support and prolonged hospitalization.1 106 107 108 118 119

National Pregnancy Registry for Atypical Antipsychotics: 866-961-2388 and .1 118 119

Lactation

Distributed into milk in humans.1 111 118 119 However, data are insufficient to determine the amount present in human milk, the effects of the drug on breast-fed infants, or the effects on milk production.118 119

Because of the potential for serious adverse reactions to aripiprazole in nursing infants, the manufacturer of aripiprazole tablets, oral solution, and the short-acting IM injection states that a decision should be made whether to discontinue nursing or the drug, taking into consideration the importance of the drug to the woman.1

The manufacturers of extended-release IM formulations of aripiprazole state that the benefit of aripiprazole therapy to the woman as well as the benefits of breast-feeding to the infant should be weighed against the potential risk to the infant from exposure to the drug or from the underlying maternal condition.118 119

Pediatric Use

Safety and efficacy of oral aripiprazole not established in pediatric patients with major depressive disorder.1 Safety and efficacy of immediate-release IM aripiprazole not established for agitation associated with schizophrenia or bipolar mania in pediatric patients.1 Safety and efficacy of extended-release IM aripiprazole and aripiprazole lauroxil not evaluated in pediatric patients <18 years of age.118 119

Safety and efficacy of oral aripiprazole for acute management of schizophrenia in pediatric patients 13–17 years of age established in a placebo-controlled study of 6 weeks' duration.1 91 Efficacy for maintenance treatment not established, but can be extrapolated from adult data and pharmacokinetic comparisons between adult and pediatric populations.1

Safety and efficacy of oral aripiprazole monotherapy for acute management of bipolar mania in pediatric patients 10–17 years of age established in a placebo-controlled study of 4 weeks' duration.1

Efficacy of oral aripiprazole as adjunctive therapy to lithium or valproate for management of manic or mixed episodes associated with bipolar disorder in pediatric patients not systematically evaluated.1 However, efficacy can be extrapolated from adult data and pharmacokinetic comparisons between adult and pediatric populations.1

Safety and efficacy of oral aripiprazole for treatment of irritability associated with autistic disorder in pediatric patients 6–17 years of age established in 2 placebo-controlled clinical studies of 8 weeks’ duration.1 109 110 Efficacy as maintenance treatment not established in a longer-term, placebo-controlled relapse prevention trial in pediatric patients 6–17 years of age.1 133

Safety and efficacy of oral aripiprazole for treatment of Tourette's syndrome in pediatric patients 6–18 years of age established in 2 short-term, placebo-controlled trials of 8 and 10 weeks' duration.1 Efficacy as maintenance therapy not systematically evaluated.1

Mean weight gain of 1.6 kg reported in pediatric patients with schizophrenia or bipolar disorder receiving oral aripiprazole compared with a gain of 0.3 kg in those receiving placebo in 2 short-term studies; from baseline to 24 weeks, mean weight gain was 5.8 kg in aripiprazole-treated patients compared with 1.4 kg in placebo recipients.1 Similar weight gain observed in short-term studies in pediatric patients with Tourette's syndrome or with irritability associated with autistic disorder.1

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).1 77 However, a later meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.79 No suicides occurred in these pediatric trials.1 77 79

Geriatric Use

Insufficient experience with oral, short-acting IM, and extended-release IM formulations of aripiprazole in patients ≥65 years of age to determine whether they respond differently than younger adults.1 118 Manufacturer states that dosage adjustment of oral and IM aripiprazole formulations based on age alone in geriatric patients is not necessary.1 118

Safety and efficacy of extended-release IM aripiprazole lauroxil not evaluated in patients >65 years of age; manufacturer makes no specific dosage recommendations for geriatric patients.119

Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death;1 28 73 113 114 118 119 increased incidence of cerebrovascular events also observed with aripiprazole.1 Aripiprazole is not approved for the treatment of patients with dementia-related psychosis.1 118 119 (See Boxed Warning, see Cerebrovascular Events in Geriatric Patients with Dementia-related Psychosis under Cautions, and see Dysphagia under Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.1 76 77 (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Poor CYP2D6 Metabolizers

Because higher plasma concentrations of aripiprazole are likely, dosage adjustment recommended for patients known to be poor metabolizers of CYP2D6.1 118 119 Approximately 8% of Caucasians and 3–8% of Blacks/African Americans cannot metabolize CYP2D6 substrates and are classified as poor CYP2D6 metabolizers.1 118 119 (See Poor CYP2D6 Metabolizer Phenotype under Dosage and Administration.)

Common Adverse Effects

Oral aripiprazole (adults): Nausea,1 vomiting,1 constipation,1 sedation,1 fatigue,1 headache,1 dizziness,1 akathisia,1 anxiety,1 insomnia,1 restlessness,1 tremor,1 extrapyramidal disorder,1 blurred vision.1

Oral aripiprazole (pediatric patients): Somnolence or sedation,1 headache,1 nausea,1 vomiting,1 tremor,1 extrapyramidal disorder,1 increased appetite,1 fatigue,1 insomnia,1 akathisia,1 nasopharyngitis,1 blurred vision,1 salivary hypersecretion,1 dizziness,1 increased weight.1

IM aripiprazole, immediate-release: Nausea.1

IM aripiprazole, extended-release: Increased weight,118 akathisia,118 injection site pain,118 sedation.118

IM aripiprazole lauroxil, extended-release: Akathisia,119 122 extrapyramidal symptoms (e.g., parkinsonism, dystonia),119 injection site reactions (e.g., pain).119 122

Interactions for Abilify

Aripiprazole is extensively metabolized in the liver principally via dehydrogenation, hydroxylation, and N-dealkylation by CYP2D6 and CYP3A4.1

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inhibitors and/or potent CYP2D6 inhibitors: Potential pharmacokinetic interaction.1

Combination of potent, moderate, and weak CYP3A4 and CYP2D6 inhibitors (e.g., potent CYP3A4 inhibitor with moderate CYP2D6 inhibitor; moderate CYP3A4 inhibitor with moderate CYP2D6 inhibitor): Potential pharmacokinetic interaction.1

Potent CYP3A4 inducers: Decreased systemic exposure to aripiprazole.1

Inhibitors or inducers of CYP isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, or 2E1: Pharmacokinetic interaction unlikely.1

Concomitant Drug

Recommended Dosage Adjustment

Potent CYP3A4 inhibitors

Oral aripiprazole: Reduce aripiprazole dosage to 50% of usual dosage; dosage adjustment not required when used as adjunctive treatment of major depressive disorder.1 Increase back to original dosage when the CYP3A4 inhibitor is discontinued.1 Further reduce dosage in patients with poor CYP2D6 metabolizer phenotype.1 (See Poor CYP2D6 Metabolizer Phenotype under Dosage and Administration.)

Extended-release IM aripiprazole injection (Abilify Maintena): Dosage adjustment not necessary if potent CYP3A4 inhibitor is added for <2 weeks.118 For concomitant therapy >14 days, reduce aripiprazole dosage from 400 to 300 mg or from 300 to 200 mg every month.118 Further dosage reduction in patients with poor CYP2D6 metabolizer phenotype may be necessary.118 (See Poor CYP2D6 Metabolizer Phenotype under Dosage and Administration.)

Extended-release IM aripiprazole lauroxil injection (Aristada): Dosage adjustment not necessary if potent CYP3A4 inhibitor is added for <2 weeks.119 For concomitant therapy >14 days, reduce aripiprazole lauroxil dosage to next available lower strength.119 Dosage reduction not necessary in patients receiving the 441-mg dosage, if tolerated.119 Reduce 882 mg every 6 weeks to 441 mg every 4 weeks.119 Further dosage reduction in patients with poor CYP2D6 metabolizer phenotype may be necessary.119 (See Poor CYP2D6 Metabolizer Phenotype under Dosage and Administration.)

Potent CYP2D6 inhibitors

Oral aripiprazole: Reduce aripiprazole dosage to 50% of usual dosage; dosage adjustment not required when used as adjunctive treatment of major depressive disorder.1 Increase back to original dosage when the CYP2D6 inhibitor is discontinued.1

Extended-release IM aripiprazole injection (Abilify Maintena): Dosage adjustment not necessary if potent CYP2D6 inhibitor is added for <2 weeks.118 For concomitant therapy >14 days, reduce aripiprazole dosage from 400 to 300 mg or from 300 to 200 mg every month.118

Extended-release IM aripiprazole lauroxil injection (Aristada): Dosage adjustment not necessary if potent CYP2D6 inhibitor is added for <2 weeks.119 For concomitant therapy >14 days, reduce aripiprazole lauroxil dosage to next available lower strength.119 Dosage reduction not necessary in patients receiving 441-mg dosage, if tolerated.119 Reduce 882 mg every 6 weeks to 441 mg every 4 weeks.119

Potent CYP3A4 inhibitors and potent CYP2D6 inhibitors

Oral aripiprazole: Reduce aripiprazole dosage to 25% of usual dosage; dosage adjustment not required when used as adjunctive treatment of major depressive disorder.1 Increase back to original dosage when the CYP3A4 and/or CYP2D6 inhibitor is discontinued.1

Extended-release IM aripiprazole injection (Abilify Maintena): Reduce aripiprazole dosage from 400 to 200 mg every month, or from 300 to 160 mg every month for concomitant therapy >14 days.118

Extended-release IM aripiprazole lauroxil injection (Aristada): Dosage adjustment not required for patients tolerating the 441-mg dosage; however, avoid concomitant use of potent CYP2D6 inhibitors and potent CYP3A4 inhibitors for >2 weeks in patients taking the 662- or 882-mg dosage.119 Dosage adjustment not required for concomitant use <2 weeks.119

Combination of potent, moderate, or weak CYP3A4 and CYP2D6 inhibitors (e.g., potent CYP3A4 inhibitor with moderate CYP2D6 inhibitor; moderate CYP3A4 inhibitor with moderate CYP2D6 inhibitor)

Oral aripiprazole: Reduce aripiprazole dosage to 25% of usual dosage, then adjust dosage to achieve clinical response.1 Increase back to original dosage when the CYP3A4 and/or CYP2D6 inhibitor is discontinued.1

Potent CYP3A4 inducers

Oral aripiprazole: Double dosage of aripiprazole over 1–2 weeks of concomitant therapy.1 Reduce back to original dosage over 1–2 weeks when the CYP3A4 inducer is discontinued.1

Extended-release IM aripiprazole injection (Abilify Maintena): Avoid use of potent CYP3A4 inducers for >14 days.118

Extended-release IM aripiprazole lauroxil injection (Aristada): Increase monthly aripiprazole dosage from 441 to 662 mg when used concomitantly for >2 weeks; dosage adjustment not required in patients receiving 662 or 882 mg every month.119 Dosage adjustment not required for concomitant use <2 weeks.119

Substrates of Hepatic Microsomal Enzymes

Substrates of CYP isoenzymes 2C9, 2C19, 2D6, and 3A4: Clinically important pharmacokinetic interaction unlikely; dosage adjustment not necessary.1 118 119

Specific Drugs

Drug

Interaction

Comments

Alcohol

Possible additive CNS effects118

Oral aripiprazole: No clinically important effects on gross motor skills or stimulus response118

Extended-release IM aripiprazole (Abilify Maintena): Manufacturer recommends avoiding concomitant use118

Specific recommendations concerning alcohol use not provided in the prescribing information for other oral and parenteral formulations of aripiprazole (e.g., Abilify, Aristada)1 119

Anticholinergic agents

Possible disruption of body temperature regulation1 118 119

Use with caution1 118 119

Benzodiazepines (e.g., lorazepam)

Possible increased sedative and orthostatic hypotensive effects1 118 119

Lorazepam: No clinically important effects on pharmacokinetics of either aripiprazole or lorazepam1 118 119

If concomitant use of aripiprazole and benzodiazepines considered necessary, monitor for excessive sedation and orthostatic hypotension; adjust dosages if needed1 118 119

Lorazepam: Routine dosage adjustment of aripiprazole and lorazepam not necessary1 118

Carbamazepine

Carbamazepine (potent CYP3A4 inducer) decreased peak plasma concentrations and AUCs of aripiprazole and dehydro-aripiprazole1 105 118 119

Oral aripiprazole: Double aripiprazole dosage over 1–2 weeks when carbamazepine is added; decrease back to original dosage over 1–2 weeks when carbamazepine is discontinued1

Extended-release aripiprazole (Abilify Maintena): Avoid concomitant use >14 days118

Extended-release aripiprazole lauroxil (Aristada): If used concomitantly >2 weeks, increase aripiprazole lauroxil dosage from 441 to 662 mg monthly; no dosage adjustment necessary for 662- or 882-mg dosages119

Clarithromycin

Clarithromycin (potent CYP3A4 inhibitor) may increase AUCs of aripiprazole and its active metabolite1

Reduce oral aripiprazole to 50% of usual dosage; if used in combination with potent CYP2D6 inhibitors, reduce oral aripiprazole dosage to 25% of usual dosage1

If used in combination with potent, moderate, and weak CYP3A4 and CYP2D6 inhibitors, initially reduce oral aripiprazole dosage to 25% of usual dosage then adjust dosage based on clinical response1

Dosage adjustment not necessary when aripiprazole used as adjunctive therapy for major depressive disorder1

Extended-release aripiprazole (Abilify Maintena): If used concomitantly >14 days, reduce aripiprazole dosage from 400 to 300 mg or from 300 to 200 mg monthly;118 if used in combination with potent CYP2D6 inhibitors, reduce dosage from 400 to 200 mg or 300 to 160 mg monthly118

Extended-release aripiprazole lauroxil (Aristada): If used concomitantly >2 weeks, reduce aripiprazole lauroxil dosage to next available lower strength; dosage reduction not necessary in patients tolerating 441-mg dosage.119 Reduce 882 mg every 6 weeks to 441 mg every 4 weeks.119 Avoid concomitant use of potent CYP3A4 inhibitors (e.g., clarithromycin) and potent CYP2D6 inhibitors for >2 weeks in patients taking the 662- or 882-mg dosages; no dosage adjustment necessary for 441-mg dosage, if tolerated119

Increase aripiprazole dosage when the CYP3A4 and/or CYP2D6 inhibitor is discontinued1

Dextromethorphan

No clinically important change in dextromethorphan (CYP2D6 and CYP3A4 substrate) pharmacokinetics observed1 118 119

Dextromethorphan dosage adjustment not necessary1 118 119

Escitalopram

No substantial effect on pharmacokinetics of escitalopram (CYP2C19 and CYP3A4 substrate)1 104

Escitalopram dosage adjustment not necessary1

Famotidine

Possible decreased peak concentration and AUC of aripiprazole; unlikely to be clinically important1

Aripiprazole dosage adjustment not necessary1

Fluoxetine

Fluoxetine (potent CYP2D6 inhibitor) expected to increase aripiprazole AUC1

Aripiprazole did not substantially affect fluoxetine pharmacokinetics1 104

Oral aripiprazole: Reduce aripiprazole to 50% of usual dosage; if used in combination with potent CYP3A4 inhibitors, reduce aripiprazole dosage to 25% of usual dosage; if used in combination with potent, moderate, or weak CYP3A4 inhibitors, reduce aripiprazole dosage to 25% of usual dosage then adjust to achieve clinical response; dosage adjustment not necessary when used as adjunctive therapy for major depressive disorder1

Extended-release aripiprazole (Abilify Maintena): If used concomitantly >14 days, reduce aripiprazole dosage from 400 to 300 mg or from 300 to 200 mg monthly; in combination with potent CYP3A4 inhibitors, reduce dosage from 400 to 200 mg or 300 to 160 mg monthly118

Extended-release aripiprazole lauroxil (Aristada): If used concomitantly >2 weeks, reduce aripiprazole lauroxil dosage to next available lower strength; no dosage adjustment necessary in patients tolerating 441-mg dosage; reduce 882 mg every 6 weeks to 441 mg every 4 weeks; dosage adjustment not necessary for concomitant use <2 weeks; avoid concomitant use of potent CYP2D6 inhibitors (e.g., fluoxetine) and potent CYP3A4 inhibitors for >2 weeks in patients taking the 662- or 882-mg dosage119

Increase aripiprazole dosage when the CYP2D6 and/or CYP3A4 inhibitor is discontinued1

Hypotensive agents

Possible additive hypotensive effects1 118 119

Use with caution; monitor BP and adjust dosage of antihypertensive agent(s), if necessary1 118 119

Itraconazole

Potent CYP3A4 inhibitors (e.g., itraconazole) may increase AUCs of aripiprazole and its active metabolite1

Reduce oral aripiprazole to 50% of usual dosage; if used in combination with potent CYP2D6 inhibitors, reduce oral aripiprazole dosage to 25% of usual dosage1

If used in combination with potent, moderate, and weak CYP3A4 and CYP2D6 inhibitors, initially reduce oral aripiprazole dosage to 25% of usual dosage then adjust dosage based on clinical response1

Dosage adjustment not necessary when aripiprazole used as adjunctive therapy for major depressive disorder1

Extended-release aripiprazole (Abilify Maintena): If used concomitantly >14 days, reduce aripiprazole dosage from 400 to 300 mg or from 300 to 200 mg monthly; if used in combination with potent CYP2D6 inhibitors, reduce dosage from 400 to 200 mg or 300 to 160 mg monthly118

Extended-release aripiprazole lauroxil (Aristada): If used concomitantly >2 weeks, reduce aripiprazole lauroxil dosage to next available lower strength; dosage reduction not necessary in patients tolerating 441-mg dosage.119 Reduce 882 mg every 6 weeks to 441 mg every 4 weeks.119 Avoid concomitant use of potent CYP3A4 inhibitors (e.g., itraconazole) and potent CYP2D6 inhibitors for >2 weeks in patients taking the 662- or 882-mg dosages; no dosage adjustment necessary for 441-mg dosage, if tolerated119

Increase aripiprazole dosage when the CYP3A4 and/or CYP2D6 inhibitor is discontinued1

Ketoconazole

Ketoconazole (potent CYP3A4 inhibitor) substantially increased AUCs of aripiprazole and its active metabolite1

Reduce oral aripiprazole to 50% of usual dosage; if used in combination with potent CYP2D6 inhibitors, reduce oral aripiprazole dosage to 25% of usual dosage1

If used in combination with potent, moderate, and weak CYP3A4 and CYP2D6 inhibitors, initially reduce oral aripiprazole dosage to 25% of usual dosage then adjust dosage based on clinical response1

Dosage adjustment not necessary when aripiprazole used as adjunctive therapy for major depressive disorder1

Extended-release aripiprazole (Abilify Maintena): If used concomitantly >14 days, reduce aripiprazole dosage from 400 to 300 mg or from 300 to 200 mg monthly; if used in combination with potent CYP2D6 inhibitors, reduce dosage from 400 to 200 mg or 300 to 160 mg monthly118

Extended-release aripiprazole lauroxil (Aristada): If used concomitantly >2 weeks, reduce aripiprazole lauroxil dosage to next available lower strength; dosage reduction not necessary in patients tolerating 441-mg dosage.119 Reduce 882 mg every 6 weeks to 441 mg every 4 weeks.119 Avoid concomitant use of potent CYP3A4 inhibitors (e.g., ketoconazole) and potent CYP2D6 inhibitors for >2 weeks in patients taking the 662- or 882-mg dosages; no dosage adjustment necessary for 441-mg dosage, if tolerated119

Increase aripiprazole dosage when the CYP3A4 and/or CYP2D6 inhibitor is discontinued1

Lamotrigine

Concomitant use with aripiprazole apparently well tolerated;92 pharmacokinetic interaction unlikely1 92

Lamotrigine dosage adjustment not necessary1 92

Lithium

Clinically important pharmacokinetic interaction unlikely1

Dosage adjustment of aripiprazole and lithium not necessary1

Omeprazole

No substantial effect on pharmacokinetics of omeprazole (CYP2C19 substrate)1

Omeprazole dosage adjustment not necessary1

Paroxetine

Paroxetine (potent CYP2D6 inhibitor) expected to increase aripiprazole AUC1

Aripiprazole did not substantially affect paroxetine pharmacokinetics1 104

Paroxetine dosage adjustment not necessary1 104

Oral aripiprazole: Reduce aripiprazole to 50% of usual dosage; if used in combination with potent CYP3A4 inhibitors, reduce aripiprazole dosage to 25% of usual dosage; if used in combination with potent, moderate, or weak CYP3A4 inhibitors, reduce aripiprazole dosage to 25% of usual dosage then adjust to achieve clinical response; dosage adjustment not necessary when used as adjunctive therapy for major depressive disorder1

Extended-release aripiprazole (Abilify Maintena): If used concomitantly >14 days, reduce aripiprazole dosage from 400 to 300 mg or from 300 to 200 mg monthly; in combination with potent CYP3A4 inhibitors, reduce dosage from 400 to 200 mg or 300 to 160 mg monthly118

Extended-release aripiprazole lauroxil (Aristada): If used concomitantly >2 weeks, reduce aripiprazole lauroxil dosage to next available lower strength; no dosage adjustment necessary in patients tolerating 441-mg dosage; reduce 882 mg every 6 weeks to 441 mg every 4 weeks; dosage adjustment not necessary for concomitant use <2 weeks; avoid concomitant use of potent CYP2D6 inhibitors (e.g., paroxetine) and potent CYP3A4 inhibitors for >2 weeks in patients taking the 662- or 882-mg dosage119

Increase aripiprazole dosage when the CYP2D6 and/or CYP3A4 inhibitor is discontinued1

Quinidine

Quinidine (potent CYP2D6 inhibitor) increased aripiprazole AUC but decreased AUC of dehydro-aripiprazole1

Oral aripiprazole: Reduce aripiprazole to 50% of usual dosage; if used in combination with potent CYP3A4 inhibitors, reduce aripiprazole dosage to 25% of usual dosage; if used in combination with potent, moderate, or weak CYP3A4 inhibitors, reduce aripiprazole dosage to 25% of usual dosage then adjust to achieve clinical response; dosage adjustment not necessary when used as adjunctive therapy for major depressive disorder1

Extended-release aripiprazole (Abilify Maintena): If used concomitantly >14 days, reduce aripiprazole dosage from 400 to 300 mg or from 300 to 200 mg monthly; in combination with potent CYP3A4 inhibitors, reduce dosage from 400 to 200 mg or 300 to 160 mg monthly118

Extended-release aripiprazole lauroxil (Aristada): If used concomitantly >2 weeks, reduce aripiprazole lauroxil dosage to next available lower strength; no dosage adjustment necessary in patients tolerating 441-mg dosage; reduce 882 mg every 6 weeks to 441 mg every 4 weeks; dosage adjustment not necessary for concomitant use <2 weeks; avoid concomitant use of potent CYP2D6 inhibitors (e.g., quinidine) and potent CYP3A4 inhibitors for >2 weeks in patients taking the 662- or 882-mg dosage119

Increase aripiprazole dosage when the CYP2D6 and/or CYP3A4 inhibitor is discontinued1

Rifampin

Potent CYP3A4 inducers expected to decrease AUCs of aripiprazole and its active metabolite1

Oral aripiprazole: Double aripiprazole dosage over 1–2 weeks when rifampin is added; decrease back to original dosage over 1–2 weeks when rifampin is discontinued1

Extended-release aripiprazole (Abilify Maintena): Avoid concomitant use >14 days118

Extended-release aripiprazole lauroxil (Aristada): If used concomitantly >2 weeks, increase aripiprazole lauroxil dosage from 441 to 662 mg monthly; no dosage adjustment necessary for 662- or 882-mg dosages119

Sertraline

Aripiprazole did not substantially affect sertraline pharmacokinetics1 104 118 119

Dosage adjustment of aripiprazole and sertraline not necessary1 118 119

Valproate

Clinically important pharmacokinetic interaction unlikely1

Dosage adjustment of aripiprazole and valproate not necessary1

Venlafaxine

No effect on pharmacokinetics of venlafaxine (CYP2D6 substrate) or O-desmethylvenlafaxine1 104

Venlafaxine dosage adjustment not necessary1

Warfarin

No clinically important effect on warfarin (CYP2C9 and CYP2C19 substrate) pharmacokinetics1

Warfarin dosage adjustment not necessary1

Before Using Abilify

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of aripiprazole in children younger than 13 years of age with schizophrenia and in children younger than 10 years of age with bipolar disorder. Safety and efficacy have not been established.

Aripiprazole is not approved for use in children or teenagers with major depression.

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of aripiprazole in children 6 to 17 years of age with autistic disorder.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of aripiprazole in elderly patients who have schizophrenia, depression, or bipolar disorder. This medicine should not be used to treat behavioral problems in elderly patients who have dementia or Alzheimer disease.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Amifampridine
  • Amisulpride
  • Bepridil
  • Bromopride
  • Cisapride
  • Dronedarone
  • Fluconazole
  • Mesoridazine
  • Metoclopramide
  • Pimozide
  • Piperaquine
  • Posaconazole
  • Saquinavir
  • Sparfloxacin
  • Terfenadine
  • Thioridazine
  • Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Alfentanil
  • Alfuzosin
  • Amiodarone
  • Amitriptyline
  • Anagrelide
  • Apomorphine
  • Arsenic Trioxide
  • Asenapine
  • Astemizole
  • Atazanavir
  • Azithromycin
  • Bedaquiline
  • Boceprevir
  • Bromazepam
  • Buprenorphine
  • Bupropion
  • Buserelin
  • Butorphanol
  • Carbamazepine
  • Ceritinib
  • Chloroquine
  • Chlorpromazine
  • Ciprofloxacin
  • Citalopram
  • Clarithromycin
  • Clomipramine
  • Clozapine
  • Cobicistat
  • Codeine
  • Conivaptan
  • Crizotinib
  • Cyclobenzaprine
  • Dabrafenib
  • Dasatinib
  • Degarelix
  • Delamanid
  • Desipramine
  • Deslorelin
  • Deutetrabenazine
  • Dihydrocodeine
  • Disopyramide
  • Dofetilide
  • Dolasetron
  • Domperidone
  • Donepezil
  • Doxepin
  • Doxylamine
  • Droperidol
  • Ebastine
  • Efavirenz
  • Enzalutamide
  • Eribulin
  • Erythromycin
  • Escitalopram
  • Famotidine
  • Felbamate
  • Fentanyl
  • Fingolimod
  • Flecainide
  • Flibanserin
  • Fluoxetine
  • Formoterol
  • Foscarnet
  • Fosphenytoin
  • Galantamine
  • Gatifloxacin
  • Gemifloxacin
  • Gonadorelin
  • Goserelin
  • Granisetron
  • Halofantrine
  • Haloperidol
  • Histrelin
  • Hydrocodone
  • Hydromorphone
  • Hydroquinidine
  • Hydroxychloroquine
  • Hydroxyzine
  • Ibutilide
  • Idelalisib
  • Iloperidone
  • Imipramine
  • Indinavir
  • Itraconazole
  • Ivabradine
  • Ketoconazole
  • Lapatinib
  • Leuprolide
  • Levofloxacin
  • Levorphanol
  • Lopinavir
  • Lumefantrine
  • Mefloquine
  • Meperidine
  • Methadone
  • Metronidazole
  • Mifepristone
  • Milnacipran
  • Mitotane
  • Mizolastine
  • Morphine
  • Morphine Sulfate Liposome
  • Moxifloxacin
  • Nafarelin
  • Nalbuphine
  • Nelfinavir
  • Netupitant
  • Nilotinib
  • Norfloxacin
  • Octreotide
  • Ofloxacin
  • Olanzapine
  • Ondansetron
  • Oxycodone
  • Oxymorphone
  • Paliperidone
  • Panobinostat
  • Paroxetine
  • Pasireotide
  • Pazopanib
  • Pentamidine
  • Periciazine
  • Perphenazine
  • Phenytoin
  • Pimavanserin
  • Pipamperone
  • Pitolisant
  • Probucol
  • Procainamide
  • Prochlorperazine
  • Promethazine
  • Propafenone
  • Protriptyline
  • Quetiapine
  • Quinidine
  • Quinine
  • Ranolazine
  • Remifentanil
  • Ribociclib
  • Rifampin
  • Rilpivirine
  • Risperidone
  • Ritonavir
  • Sertindole
  • Sevoflurane
  • Sodium Phosphate
  • Sodium Phosphate, Dibasic
  • Sodium Phosphate, Monobasic
  • Solifenacin
  • Sorafenib
  • Sotalol
  • St John's Wort
  • Sufentanil
  • Sulpiride
  • Sunitinib
  • Tacrolimus
  • Tamoxifen
  • Tapentadol
  • Telaprevir
  • Telavancin
  • Telithromycin
  • Tetrabenazine
  • Tizanidine
  • Tolterodine
  • Toremifene
  • Tramadol
  • Trazodone
  • Trimipramine
  • Triptorelin
  • Vandetanib
  • Vardenafil
  • Vemurafenib
  • Venlafaxine
  • Vilanterol
  • Vinflunine
  • Voriconazole
  • Vorinostat
  • Zuclopenthixol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Alcohol abuse, history of or
  • Depression or
  • Diabetes, or family history of or
  • Drug abuse or dependence, history of or
  • Hyperglycemia (high blood sugar) or
  • Neuroleptic malignant syndrome (NMS), history of or
  • Neutropenia (low white blood cells) or
  • Seizures, history of—Use with caution. May make these conditions worse.
  • Blood vessel disease or
  • Dehydration or
  • Heart attack or stroke, history of or
  • Heart disease or
  • Heart failure or
  • Heart rhythm problems or
  • Hypotension (low blood pressure) or
  • Hypovolemia (decrease in blood volume) or
  • Ischemic heart disease, history of or
  • Trouble with swallowing—Use with caution. May cause side effects to become worse.
  • Phenylketonuria (PKU)—The orally disintegrating tablet contains phenylalanine, which can make this condition worse.

Abilify Dosage and Administration

Schizophrenia

Adults

The recommended starting and target dose for Abilify is 10 or 15 mg/day administered on a once-a-day schedule without regard to meals. Abilify has been systematically evaluated and shown to be effective in a dose range of 10 to 30 mg/day, when administered as the tablet formulation; however, doses higher than 10 or 15 mg/day were not more effective than 10 or 15 mg/day. Dosage increases should generally not be made before 2 weeks, the time needed to achieve steady-state [see CLINICAL STUDIES (14.1)].

Maintenance Treatment: Maintenance of efficacy in schizophrenia was demonstrated in a trial involving patients with schizophrenia who had been symptomatically stable on other antipsychotic medications for periods of 3 months or longer. These patients were discontinued from those medications and randomized to either Abilify 15 mg/day or placebo, and observed for relapse [see CLINICAL STUDIES (14.1)]. Patients should be periodically reassessed to determine the continued need for maintenance treatment.

Adolescents

The recommended target dose of Abilify is 10 mg/day. Aripiprazole was studied in adolescent patients 13 to 17 years of age with schizophrenia at daily doses of 10 mg and 30 mg. The starting daily dose of the tablet formulation in these patients was 2 mg, which was titrated to 5 mg after 2 days and to the target dose of 10 mg after 2 additional days. Subsequent dose increases should be administered in 5 mg increments. The 30 mg/day dose was not shown to be more efficacious than the 10 mg/day dose. Abilify can be administered without regard to meals [see CLINICAL STUDIES (14.1)]. Patients should be periodically reassessed to determine the need for maintenance treatment.

Switching from Other Antipsychotics

There are no systematically collected data to specifically address switching patients with schizophrenia from other antipsychotics to Abilify or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized.

Bipolar I Disorder

Acute Treatment of Manic and Mixed Episodes

Adults: The recommended starting dose in adults is 15 mg given once daily as monotherapy and 10 mg to 15 mg given once daily as adjunctive therapy with lithium or valproate. Abilify can be given without regard to meals. The recommended target dose of Abilify is 15 mg/day, as monotherapy or as adjunctive therapy with lithium or valproate. The dose may be increased to 30 mg/day based on clinical response. The safety of doses above 30 mg/day has not been evaluated in clinical trials.

Pediatrics: The recommended starting dose in pediatric patients (10 to 17 years) as monotherapy is 2 mg/day, with titration to 5 mg/day after 2 days, and a target dose of 10 mg/day after 2 additional days. Recommended dosing as adjunctive therapy to lithium or valproate is the same. Subsequent dose increases, if needed, should be administered in 5 mg/day increments. Abilify can be given without regard to meals [see CLINICAL STUDIES (14.2)].

Adjunctive Treatment of Major Depressive Disorder

Adults

The recommended starting dose for Abilify as adjunctive treatment for patients already taking an antidepressant is 2 to 5 mg/day. The recommended dosage range is 2 to 15 mg/day. Dosage adjustments of up to 5 mg/day should occur gradually, at intervals of no less than 1 week [see CLINICAL STUDIES (14.3)]. Patients should be periodically reassessed to determine the continued need for maintenance treatment.

Irritability Associated with Autistic Disorder

Pediatric Patients (6 to 17 years)

The recommended dosage range for the treatment of pediatric patients with irritability associated with autistic disorder is 5 to 15 mg/day.

Dosing should be initiated at 2 mg/day. The dose should be increased to 5 mg/day, with subsequent increases to 10 or 15 mg/day if needed. Dose adjustments of up to 5 mg/day should occur gradually, at intervals of no less than 1 week [see CLINICAL STUDIES (14.4)]. Patients should be periodically reassessed to determine the continued need for maintenance treatment.

Tourette’s Disorder

Pediatric Patients (6 to 18 years)

The recommended dosage range for Tourette’s Disorder is 5 to 20 mg/day.

For patients weighing less than 50 kg, dosing should be initiated at 2 mg/day with a target dose of 5 mg/day after 2 days. The dose can be increased to 10 mg/day in patients who do not achieve optimal control of tics. Dosage adjustments should occur gradually at intervals of no less than 1 week.

For patients weighing 50 kg or more, dosing should be initiated at 2 mg/day for 2 days, and then increased to 5 mg/day for 5 days, with a target dose of 10 mg/day on day 8. The dose can be increased up to 20 mg/day for patients who do not achieve optimal control of tics. Dosage adjustments should occur gradually in increments of 5 mg/day at intervals of no less than 1 week. [see CLINICAL STUDIES (14.5)].

Patients should be periodically reassessed to determine the continued need for maintenance treatment.

Agitation Associated with Schizophrenia or Bipolar Mania (Intramuscular Injection)

Adults

The recommended dose in these patients is 9.75 mg. The recommended dosage range is 5.25 to 15 mg. No additional benefit was demonstrated for 15 mg compared to 9.75 mg. A lower dose of 5.25 mg may be considered when clinical factors warrant. If agitation warranting a second dose persists following the initial dose, cumulative doses up to a total of 30 mg/day may be given. However, the efficacy of repeated doses of Abilify injection in agitated patients has not been systematically evaluated in controlled clinical trials. The safety of total daily doses greater than 30 mg or injections given more frequently than every 2 hours have not been adequately evaluated in clinical trials [see CLINICAL STUDIES (14.6)].

If ongoing Abilify therapy is clinically indicated, oral Abilify in a range of 10 to 30 mg/day should replace Abilify injection as soon as possible [see DOSAGE AND ADMINISTRATION (2.1 and 2.2)].

Administration of Abilify Injection

To administer Abilify Injection, draw up the required volume of solution into the syringe as shown in Table 1. Discard any unused portion.

Table 1: Abilify Injection Dosing Recommendations

Single-Dose

Required Volume of Solution

5.25 mg

0.7 mL

9.75 mg

1.3 mL

15 mg

2 mL

Abilify Injection is intended for intramuscular use only. Do not administer intravenously or subcutaneously. Inject slowly, deep into the muscle mass.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Dosage Adjustments for Cytochrome P450 Considerations

Dosage adjustments are recommended in patients who are known CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors or strong CYP3A4 inducers (see Table 2). When the coadministered drug is withdrawn from the combination therapy, Abilify dosage should then be adjusted to its original level. When the coadministered CYP3A4 inducer is withdrawn, Abilify dosage should be reduced to the original level over 1 to 2 weeks. Patients who may be receiving a combination of strong, moderate, and weak inhibitors of CYP3A4 and CYP2D6 (e.g., a strong CYP3A4 inhibitor and a moderate CYP2D6 inhibitor or a moderate CYP3A4 inhibitor with a moderate CYP2D6 inhibitor), the dosing may be reduced to one-quarter (25%) of the usual dose initially and then adjusted to achieve a favorable clinical response.

Table 2: Dose Adjustments for Abilify in Patients who are known CYP2D6 Poor Metabolizers and Patients Taking Concomitant CYP2D6 Inhibitors, 3A4 Inhibitors, and/or CYP3A4 Inducers

Factors

Dosage Adjustments for Abilify

Known CYP2D6 Poor Metabolizers

Administer half of usual dose

Known CYP2D6 Poor Metabolizers taking concomitant strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin)

Administer a quarter of usual dose

Strong CYP2D6 (e.g., quinidine, fluoxetine, paroxetine) or CYP3A4 inhibitors (e.g., itraconazole, clarithromycin)

Administer half of usual dose

Strong CYP2D6 and CYP3A4 inhibitors

Administer a quarter of usual dose

Strong CYP3A4 inducers (e.g., carbamazepine, rifampin)

Double usual dose over 1 to 2 weeks

When adjunctive Abilify is administered to patients with major depressive disorder, Abilify should be administered without dosage adjustment as specified in DOSAGE AND ADMINISTRATION (2.3).

Dosing of Oral Solution

The oral solution can be substituted for tablets on a mg-per-mg basis up to the 25 mg dose level. Patients receiving 30 mg tablets should receive 25 mg of the solution [see CLINICAL PHARMACOLOGY (12.3)].

Dosing of Orally Disintegrating Tablets

The dosing for Abilify Orally Disintegrating Tablets is the same as for the oral tablets [see DOSAGE AND ADMINISTRATION (2.1, 2.2, 2.3, and 2.4)].

Contraindications

Abilify is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis [see ADVERSE REACTIONS (6.2)].

Abilify Description

Aripiprazole is a psychotropic drug that is available as Abilify® (aripiprazole) Tablets, Abilify DISCMELT® (aripiprazole) Orally Disintegrating Tablets, Abilify® (aripiprazole) Oral Solution, and Abilify® (aripiprazole) Injection, a solution for intramuscular injection. Aripiprazole is 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydrocarbostyril. The empirical formula is C23H27Cl2N3O2 and its molecular weight is 448.38. The chemical structure is:

Abilify Tablets are available in 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg strengths. Inactive ingredients include cornstarch, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. Colorants include ferric oxide (yellow or red) and FD&C Blue No. 2 Aluminum Lake.

Abilify DISCMELT Orally Disintegrating Tablets are available in 10 mg and 15 mg strengths. Inactive ingredients include acesulfame potassium, aspartame, calcium silicate, croscarmellose sodium, crospovidone, crème de vanilla (natural and artificial flavors), magnesium stearate, microcrystalline cellulose, silicon dioxide, tartaric acid, and xylitol. Colorants include ferric oxide (yellow or red) and FD&C Blue No. 2 Aluminum Lake.

Abilify Oral Solution is a clear, colorless to light-yellow solution available in a concentration of 1 mg/mL. The inactive ingredients for this solution include disodium edetate, fructose, glycerin, dl-lactic acid, methylparaben, propylene glycol, propylparaben, sodium hydroxide, sucrose, and purified water. The oral solution is flavored with natural orange cream and other natural flavors.

Abilify Injection is available in single-dose vials as a ready-to-use, 9.75 mg/1.3 mL (7.5 mg/mL) clear, colorless, sterile, aqueous solution for intramuscular use only. Inactive ingredients for this solution include 199.5 mg of sulfobutylether β-cyclodextrin (SBECD), 10.4 mg of tartaric acid, qs to pH 4.3 of sodium hydroxide, and qs to 1.33 mL of water for injection.

Is this medication available as a generic drug?

Yes, this medication is available in generic form.

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Reviewed on 5/1/2017 References REFERENCES:

Food and Drug Administration (FDA) aripiprazole patient packaging information. Revised: Dec 2014. ABILIFY is a trademark of Otsuka Pharmaceutical Company.
<https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021436s038,021713s030,021729s022,021866s023lbl.pdf>

Medscape. "aripiprazole (Rx)."
<https://reference.medscape.com/drug/abilify-maintena-aristada-aripiprazole-342983>

Food and Drug Administration. "FDA Drug Safety Communication: FDA warns about new impulse-control problems associated with mental health drug aripiprazole (Abilify, Abilify Maintena, Aristada)." Updated: Jun 07, 2016.
<https://www.fda.gov/Drugs/DrugSafety/ucm498662.htm>

Brand names

  • Abilify®

How supplied

Dosage Forms And Strengths

ABILIFY® (aripiprazole) Tablets are available as described in Table 3.

Table 3: ABILIFY Tablet Presentations

Tablet Strength Tablet Color/Shape Tablet Markings
2 mg green “A-006”
modified rectangle and “2”
5 mg blue “A-007”
modified rectangle and “5”
10 mg pink “A-008”
modified rectangle and “10”
15 mg yellow “A-009”
round and “15”
20 mg white “A-010”
round and “20”
30 mg pink “A-011”
round and “30”

ABILIFY DISCMELT® (aripiprazole) Orally Disintegrating Tablets are available as described in Table 4.

Table 4: ABILIFY DISCMELT Orally Disintegrating Tablet Presentations

Tablet Strength Tablet Color/Shape Tablet Markings
10 mg pink (with scattered specks) “A” and “640”
round “10”
15 mg yellow (with scattered specks) “A” and “641”
round “15”

ABILIFY® (aripiprazole) Oral Solution (1 mg/mL) is a clear, colorless to light-yellow solution, supplied in child-resistant bottles along with a calibrated oral dosing cup.

ABILIFY® (aripiprazole) Injection for Intramuscular Use is a clear, colorless solution available as a ready-to-use, 9.75 mg/1.3 mL (7.5 mg/mL) solution in clear, Type 1 glass vials.

Storage And Handling

ABILIFY® (aripiprazole) Tablets have markings on one side and are available in the strengths and packages listed in Table 32.

Table 32: ABILIFY Tablet Presentations

Tablet Strength Tablet Color/Shape Tablet Markings Pack Size NDC Code
2 mg green modified rectangle “A-006” and “2” Bottle of 30 59148-006-13
5 mg blue “A-007” Bottle of 30 59148-007-13
modified rectangle and “5” Blister of 100 59148-007-35
10 mg pink “A-008” Bottle of 30 59148-008-13
modified rectangle and “10” Blister of 100 59148-008-35
15 mg yellow “A-009” Bottle of 30 59148-009-13
round and “15” Blister of 100 59148-009-35
20 mg white “A-010” Bottle of 30 59148-010-13
round and “20” Blister of 100 59148-010-35
30 mg pink “A-011” Bottle of 30 59148-011-13
round and “30” Blister of 100 59148-011-35

ABILIFY DISCMELT® (aripiprazole) Orally Disintegrating Tablets are round tablets with markings on either side. ABILIFY DISCMELT is available in the strengths and packages listed in Table 33.

Table 33: ABILIFY DISCMELT Orally Disintegrating Tablet Presentations

Tablet Strength Tablet Color Tablet Markings Pack Size NDC Code
10 mg pink (with scattered specks) “A” and “640” “10” Blister of 30 59148-640-23
15 mg yellow (with scattered specks) “A” and “641” “15” Blister of 30 59148-641-23

ABILIFY® (aripiprazole) Oral Solution (1 mg/mL) is supplied in child-resistant bottles along with a calibrated oral dosing cup. ABILIFY Oral Solution is available as follows:

150 mL bottle NDC 59148-013-15

ABILIFY® (aripiprazole) Injection for intramuscular use is available as a ready-to-use, 9.75 mg/1.3 mL (7.5 mg/mL) solution in clear, Type 1 glass vials as follows:

9.75 mg/1.3 mL single-dose vial NDC 59148-016-65

Storage

Tablets

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .

Oral Solution

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Opened bottles of ABILIFY Oral Solution can be used for up to 6 months after opening, but not beyond the expiration date on the bottle. The bottle and its contents should be discarded after the expiration date.

Injection

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light by storing in the original container. Retain in carton until time of use.

Tablets manufactured by Otsuka Pharmaceutical Co., Ltd., Tokyo, 101-8535 Japan. Orally Disintegrating Tablets, Oral Solution, and Injection manufactured by Bristol-Myers Squibb Company, Princeton, NJ 08543 USA. Distributed and marketed by Otsuka America Pharmaceutical, Inc., Rockville, MD 20850 USA. Revised: Aug 2016

Side effects

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reactions are discussed in more detail in other sections of the labeling:

  • Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
  • Cerebrovascular Adverse Events, Including Stroke [see WARNINGS AND PRECAUTIONS]
  • Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
  • Neuroleptic Malignant Syndrome (NMS) [see WARNINGS AND PRECAUTIONS]
  • Tardive Dyskinesia [see WARNINGS AND PRECAUTIONS]
  • Metabolic Changes [see WARNINGS AND PRECAUTIONS]
  • Pathological Gambling and Other Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
  • Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
  • Leukopenia, Neutropenia, and Agranulocytosis [see WARNINGS AND PRECAUTIONS]
  • Seizures/Convulsions [see WARNINGS AND PRECAUTIONS]
  • Potential for Cognitive and Motor Impairment [see WARNINGS AND PRECAUTIONS]
  • Body Temperature Regulation [see WARNINGS AND PRECAUTIONS]
  • Suicide [see WARNINGS AND PRECAUTIONS]
  • Dysphagia [see WARNINGS AND PRECAUTIONS]

The most common adverse reactions in adult patients in clinical trials ( ≥ 10%) were nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, insomnia, and restlessness.

The most common adverse reactions in the pediatric clinical trials ( ≥ 10%) were somnolence, headache, vomiting, extrapyramidal disorder, fatigue, increased appetite, insomnia, nausea, nasopharyngitis, and weight increased.

ABILIFY has been evaluated for safety in 13,543 adult patients who participated in multiple-dose, clinical trials in schizophrenia, bipolar disorder, major depressive disorder, Dementia of the Alzheimer's type, Parkinson's disease, and alcoholism, and who had approximately 7619 patient-years of exposure to oral ABILIFY and 749 patients with exposure to ABILIFY injection. A total of 3390 patients were treated with oral ABILIFY for at least 180 days and 1933 patients treated with oral ABILIFY had at least 1 year of exposure.

ABILIFY has been evaluated for safety in 1,686 patients (6 to 18 years) who participated in multiple-dose, clinical trials in schizophrenia, bipolar mania, autistic disorder, or Tourette's disorder and who had approximately 1,342 patient-years of exposure to oral ABILIFY. A total of 959 pediatric patients were treated with oral ABILIFY for at least 180 days and 556 pediatric patients treated with oral ABILIFY had at least 1 year of exposure.

The conditions and duration of treatment with ABILIFY (monotherapy and adjunctive therapy with antidepressants or mood stabilizers) included (in overlapping categories) double-blind, comparative and noncomparative open-label studies, inpatient and outpatient studies, fixed-and flexible-dose studies, and short-and longer-term exposure.

Clinical Trials Experience

Adult Patients With Schizophrenia

The following findings are based on a pool of five placebo-controlled trials (four 4-week and one 6-week) in which oral ABILIFY was administered in doses ranging from 2 to 30 mg/day.

Commonly Observed Adverse Reactions

The only commonly observed adverse reaction associated with the use of ABILIFY in patients with schizophrenia (incidence of 5% or greater and

ABILIFY incidence at least twice that for placebo) was akathisia (ABILIFY 8%; placebo 4%).

Adult Patients With Bipolar Mania

Monotherapy

The following findings are based on a pool of 3-week, placebo-controlled, bipolar mania trials in which oral ABILIFY was administered at doses of 15 or 30 mg/day.

Commonly Observed Adverse Reactions

Commonly observed adverse reactions associated with the use of ABILIFY in patients with bipolar mania (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) are shown in Table 16.

Table 16: Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials of Adult Patients with Bipolar Mania Treated with Oral ABILIFY Monotherapy

Preferred Term Percentage of Patients Reporting Reaction
ABILIFY
(n=917)
Placebo
(n=753)
Akathisia 13 4
Sedation 8 3
Restlessness 6 3
Tremor 6 3
Extrapyramidal Disorder 5 2

Less Common Adverse Reactions In Adults

Table 17 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (up to 6 weeks in schizophrenia and up to 3 weeks in bipolar mania), including only those reactions that occurred in 2% or more of patients treated with ABILIFY (doses ≥ 2 mg/day) and for which the incidence in patients treated with ABILIFY was greater than the incidence in patients treated with placebo in the combined dataset.

Table 17: Adverse Reactions in Short-Term, Placebo-Controlled Trials in Adult Patients Treated with Oral ABILIFY

System Organ Class
Preferred Term
Percentage of Patients Reporting Reactiona
ABILIFY
(n=1843)
Placebo
(n=1166)
Eye Disorders
  Blurred Vision 3 1
Gastrointestinal Disorders
  Nausea 15 11
  Constipation 11 7
  Vomiting 11 6
  Dyspepsia 9 7
  Dry Mouth 5 4
  Toothache 4 3
  Abdominal Discomfort 3 2
  Stomach Discomfort 3 2
General Disorders and Administration Site Conditions
  Fatigue 6 4
  Pain 3 2
Musculoskeletal and Connective Tissue Disorders
  Musculoskeletal Stiffness 4 3
  Pain in Extremity 4 2
  Myalgia 2 1
  Muscle Spasms 2 1
Nervous System Disorders
  Headache 27 23
  Dizziness 10 7
  Akathisia 10 4
  Sedation 7 4
  Extrapyramidal Disorder 5 3
  Tremor 5 3
  Somnolence 5 3
Psychiatric Disorders
  Agitation 19 17
  Insomnia 18 13
  Anxiety 17 13
  Restlessness 5 3
Respiratory, Thoracic, and Mediastinal Disorders
  Pharyngolaryngeal Pain 3 2
  Cough 3 2
a Adverse reactions reported by at least 2% of patients treated with oral ABILIFY, except adverse reactions which had an incidence equal to or less than placebo.

An examination of population subgroups did not reveal any clear evidence of differential adverse reaction incidence on the basis of age, gender, or race.

Adult Patients With Adjunctive Therapy With Bipolar Mania

The following findings are based on a placebo-controlled trial of adult patients with bipolar disorder in which ABILIFY was administered at doses of 15 or 30 mg/day as adjunctive therapy with lithium or valproate.

Adverse Reactions Associated with Discontinuation of Treatment

In a study of patients who were already tolerating either lithium or valproate as monotherapy, discontinuation rates due to adverse reactions were 12% for patients treated with adjunctive ABILIFY compared to 6% for patients treated with adjunctive placebo. The most common adverse drug reactions associated with discontinuation in the adjunctive ABILIFY-treated compared to placebo-treated patients were akathisia (5% and 1%, respectively) and tremor (2% and 1%, respectively).

Commonly Observed Adverse Reactions

The commonly observed adverse reactions associated with adjunctive ABILIFY and lithium or valproate in patients with bipolar mania (incidence of 5% or greater and incidence at least twice that for adjunctive placebo) were: akathisia, insomnia, and extrapyramidal disorder.

Less Common Adverse Reactions In Adult Patients With Adjunctive Therapy In Bipolar Mania

Table 18 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during acute treatment (up to 6 weeks), including only those reactions that occurred in 2% or more of patients treated with adjunctive ABILIFY (doses of 15 or 30 mg/day) and lithium or valproate and for which the incidence in patients treated with this combination was greater than the incidence in patients treated with placebo plus lithium or valproate.

Table 18: Adverse Reactions in a Short-Term, Placebo-Controlled Trial of Adjunctive Therapy in Patients with Bipolar Disorder

System Organ Class
Preferred Term
Percentage of Patients Reporting Reactiona
ABILIFY + Li or Val*
(n=253)
Placebo + Li or Val*
(n=130)
Gastrointestinal Disorders
  Nausea 8 5
  Vomiting 4 0
  Salivary Hypersecretion 4 2
  Dry Mouth 2 1
Infections and Infestations
  Nasopharyngitis 3 2
Investigations
  Weight Increased 2 1
Nervous System Disorders
  Akathisia 19 5
  Tremor 9 6
  Extrapyramidal Disorder 5 1
  Dizziness 4 1
  Sedation 4 2
Psychiatric Disorders
  Insomnia 8 4
  Anxiety 4 1
  Restlessness 2 1
a Adverse reactions reported by at least 2% of patients treated with oral ABILIFY, except adverse reactions which had an incidence equal to or less than placebo.
* Lithium or Valproate

Pediatric Patients (13 to 17 years) With Schizophrenia

The following findings are based on one 6-week, placebo-controlled trial in which oral ABILIFY was administered in doses ranging from 2 to 30 mg/day.

Adverse Reactions Associated with Discontinuation of Treatment

The incidence of discontinuation due to adverse reactions between ABILIFY-treated and placebo-treated pediatric patients (13 to 17 years) was 5% and 2%, respectively.

Commonly Observed Adverse Reactions

Commonly observed adverse reactions associated with the use of ABILIFY in adolescent patients with schizophrenia (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) were extrapyramidal disorder, somnolence, and tremor.

Pediatric Patients (10 to 17 years) With Bipolar Mania

The following findings are based on one 4-week, placebo-controlled trial in which oral ABILIFY was administered in doses of 10 or 30 mg/day.

Adverse Reactions Associated with Discontinuation of Treatment

The incidence of discontinuation due to adverse reactions between ABILIFY-treated and placebo-treated pediatric patients (10 to 17 years) was 7% and 2%, respectively.

Commonly Observed Adverse Reactions

Commonly observed adverse reactions associated with the use of ABILIFY in pediatric patients with bipolar mania (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) are shown in Table 19.

Table 19: Commonly Observed Adverse Reactions in Short- Term, Placebo-Controlled Trials of Pediatric Patients(10 to 17 years) with Bipolar Mania Treated with Oral ABILIFY

Preferred Term Percentage of Patients Reporting Reaction
ABILIFY
(n=197)
Placebo
(n=97)
Somnolence 23 3
Extrapyramidal Disorder 20 3
Fatigue 11 4
Nausea 11 4
Akathisia 10 2
Blurred Vision 8 0
Salivary Hypersecretion 6 0
Dizziness 5 1

Pediatric Patients (6 to 17 years) With Autistic Disorder

The following findings are based on two 8-week, placebo-controlled trials in which oral ABILIFY was administered in doses of 2 to 15 mg/day.

Adverse Reactions Associated with Discontinuation of Treatment

The incidence of discontinuation due to adverse reactions between ABILIFY-treated and placebo-treated pediatric patients (6 to 17 years) was 10% and 8%, respectively.

Commonly Observed Adverse Reactions

Commonly observed adverse reactions associated with the use of ABILIFY in pediatric patients with autistic disorder (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) are shown in Table 20.

Table 20: Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials of Pediatric Patients (6 to 17 years) with Autistic Disorder Treated with Oral ABILIFY

Preferred Term Percentage of Patients Reporting Reaction
ABILIFY
(n=212)
Placebo
(n=101)
Sedation 21 4
Fatigue 17 2
Vomiting 14 7
Somnolence 10 4
Tremor 10 0
Pyrexia 9 1
Drooling 9 0
Decreased Appetite 7 2
Salivary Hypersecretion 6 1
Extrapyramidal Disorder 6 0
Lethargy 5 0

Pediatric Patients (6 to 18 years) With Tourette's Disorder

The following findings are based on one 8-week and one 10-week, placebo-controlled trials in which oral ABILIFY was administered in doses of 2 to 20 mg/day.

Adverse Reactions Associated with Discontinuation of Treatment

The incidence of discontinuation due to adverse reactions between ABILIFY-treated and placebo-treated pediatric patients (6 to 18 years) was 7% and 1%, respectively.

Commonly Observed Adverse Reactions

Commonly observed adverse reactions associated with the use of ABILIFY in pediatric patients with Tourette's disorder (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) are shown in Table 21.

Table 21: Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials of Pediatric Patients (6 to 18 years) with Tourette's Disorder Treated with Oral ABILIFY

Preferred Term Percentage of Patients Reporting Reaction
ABILIFY
(n=121)
Placebo
(n=72)
Sedation 13 6
Somnolence 13 1
Nausea 11 4
Headache 10 3
Nasopharyngitis 9 0
Fatigue 8 0
Increased Appetite 7 1

Less Common Adverse Reactions In Pediatric Patients (6 to 18 years) With Schizophrenia, Bipolar Mania, Autistic Disorder, Or Tourette's Disorder

Table 22 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (up to 6 weeks in schizophrenia, up to 4 weeks in bipolar mania, up to 8 weeks in autistic disorder, and up to 10 weeks in Tourette's disorder), including only those reactions that occurred in 2% or more of pediatric patients treated with ABILIFY (doses ≥ 2 mg/day) and for which the incidence in patients treated with ABILIFY was greater than the incidence in patients treated with placebo.

Table 22: Adverse Reactions in Short-Term, Placebo-Controlled Trials of Pediatric Patients (6 to 18 years) Treated with Oral ABILIFY

System Organ Class
Preferred Term
Percentage of Patients Reporting Reactiona
ABILIFY
(n=732)
Placebo
(n=370)
Eye Disorders
  Blurred Vision 3 0
Gastrointestinal Disorders
  Abdominal Discomfort 2 1
  Vomiting 8 7
  Nausea 8 4
  Diarrhea 4 3
  Salivary Hypersecretion 4 1
  Abdominal Pain Upper 3 2
  Constipation 2 2
General Disorders and Administration Site Conditions
  Fatigue 10 2
  Pyrexia 4 1
  Irritability 2 1
  Asthenia 2 1
Infections and Infestations
  Nasopharyngitis 6 3
  Investigations
  Weight Increased 3 1
Metabolism and Nutrition Disorders
  Increased Appetite 7 3
  Decreased Appetite 5 4
Musculoskeletal and Connective Tissue Disorders
  Musculoskeletal Stiffness 2 1
  Muscle Rigidity 2 1
Nervous System Disorders
  Somnolence 16 4
  Headache 12 10
  Sedation 9 2
  Tremor 9 1
  Extrapyramidal Disorder 6 1
  Akathisia 6 4
  Drooling 3 0
  Lethargy 3 0
  Dizziness 3 2
  Dystonia 2 1
Respiratory, Thoracic, and Mediastinal Disorders
  Epistaxis 2 1
Skin and Subcutaneous Tissue Disorders
  Rash 2 1
a Adverse reactions reported by at least 2% of pediatric patients treated with oral ABILIFY, except adverse reactions which had an incidence equal to or less than placebo.

Adult Patients Receiving ABILIFY As Adjunctive Treatment Of Major Depressive Disorder

The following findings are based on a pool of two placebo-controlled trials of patients with major depressive disorder in which ABILIFY was administered at doses of 2 mg to 20 mg as adjunctive treatment to continued antidepressant therapy.

Adverse Reactions Associated with Discontinuation of Treatment

The incidence of discontinuation due to adverse reactions was 6% for adjunctive ABILIFY-treated patients and 2% for adjunctive placebo-treated patients.

Commonly Observed Adverse Reactions

The commonly observed adverse reactions associated with the use of adjunctive ABILIFY in patients with major depressive disorder (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo) were: akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision.

Less Common Adverse Reactions in Adult Patients with Major Depressive Disorder

Table 23 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (up to 6 weeks), including only those adverse reactions that occurred in 2% or more of patients treated with adjunctive ABILIFY (doses ≥ 2 mg/day) and for which the incidence in patients treated with adjunctive ABILIFY was greater than the incidence in patients treated with adjunctive placebo in the combined dataset.

Table 23: Adverse Reactions in Short-Term, Placebo-Controlled Adjunctive Trials in Patients with Major Depressive Disorder

System Organ Class
Preferred Term
Percentage of Patients Reporting Reactiona
ABILIFY + ADT*
(n=371)
Placebo + ADT*
(n=366)
Eye Disorders
  Blurred Vision 6 1
Gastrointestinal Disorders
  Constipation 5 2
General Disorders and Administration Site Conditions
  Fatigue 8 4
  Feeling Jittery 3 1
Infections and Infestations
  Upper Respiratory Tract Infection 6 4
Investigations
  Weight Increased 3 2
Metabolism and Nutrition Disorders
  Increased Appetite 3 2
Musculoskeletal and Connective Tissue Disorders
  Arthralgia 4 3
  Myalgia 3 1
Nervous System Disorders
  Akathisia 25 4
  Somnolence 6 4
  Tremor 5 4
  Sedation 4 2
  Dizziness 4 2
  Disturbance in Attention 3 1
  Extrapyramidal Disorder 2 0
Psychiatric Disorders
  Restlessness 12 2
  Insomnia 8 2
a Adverse reactions reported by at least 2% of patients treated with adjunctive ABILIFY, except adverse reactions which had an incidence equal to or less than placebo.
* Antidepressant Therapy

Patients With Agitation Associated With Schizophrenia Or Bipolar Mania (Intramuscular Injection)

The following findings are based on a pool of three placebo-controlled trials of patients with agitation associated with schizophrenia or bipolar mania in which ABILIFY injection was administered at doses of 5.25 mg to 15 mg.

Commonly Observed Adverse Reactions

There was one commonly observed adverse reaction (nausea) associated with the use of ABILIFY injection in patients with agitation associated with schizophrenia and bipolar mania (incidence of 5% or greater and ABILIFY incidence at least twice that for placebo).

Less Common Adverse Reactions in Patients with Agitation Associated with Schizophrenia or Bipolar Mania

Table 24 enumerates the pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (24-hour), including only those adverse reactions that occurred in 2% or more of patients treated with ABILIFY injection (doses ≥ 5.25 mg/day) and for which the incidence in patients treated with ABILIFY injection was greater than the incidence in patients treated with placebo in the combined dataset.

Table 24: Adverse Reactions in Short-Term, Placebo-Controlled Trials in Patients Treated with ABILIFY Injection

System Organ Class
Preferred Term
Percentage of Patients Reporting Reactiona
ABILIFY
(n=501)
Placebo
(n=220)
Cardiac Disorders
  Tachycardia 2 < 1
Gastrointestinal Disorders
  Nausea 9 3
  Vomiting 3 1
General Disorders and Administration Site Conditions
  Fatigue 2 1
Nervous System Disorders
  Headache 12 7
  Dizziness 8 5
  Somnolence 7 4
  Sedation 3 2
  Akathisia 2 0
a Adverse reactions reported by at least 2% of patients treated with ABILIFY injection, except adverse reactions which had an incidence equal to or less than placebo.

Dose-Related Adverse Reactions

Schizophrenia

Dose response relationships for the incidence of treatment-emergent adverse events were evaluated from four trials in adult patients with schizophrenia comparing various fixed doses (2, 5, 10, 15, 20, and 30 mg/day) of oral ABILIFY to placebo. This analysis, stratified by study, indicated that the only adverse reaction to have a possible dose response relationship, and then most prominent only with 30 mg, was somnolence [including sedation]; (incidences were placebo, 7.1%; 10 mg, 8.5%; 15 mg, 8.7%; 20 mg, 7.5%; 30 mg, 12.6%).

In the study of pediatric patients (13 to 17 years of age) with schizophrenia, three common adverse reactions appeared to have a possible dose response relationship: extrapyramidal disorder (incidences were placebo, 5.0%; 10 mg, 13.0%; 30 mg, 21.6%); somnolence (incidences were placebo, 6.0%; 10 mg, 11.0%; 30 mg, 21.6%); and tremor (incidences were placebo, 2.0%; 10 mg, 2.0%; 30 mg, 11.8%).

Bipolar Mania

In the study of pediatric patients (10 to 17 years of age) with bipolar mania, four common adverse reactions had a possible dose response relationship at 4 weeks; extrapyramidal disorder (incidences were placebo, 3.1%; 10 mg, 12.2%; 30 mg, 27.3%); somnolence (incidences were placebo, 3.1%; 10 mg, 19.4%; 30 mg, 26.3%); akathisia (incidences were placebo, 2.1%; 10 mg, 8.2%; 30 mg, 11.1%); and salivary hypersecretion (incidences were placebo, 0%; 10 mg, 3.1%; 30 mg, 8.1%).

Autistic Disorder

In a study of pediatric patients (6 to 17 years of age) with autistic disorder, one common adverse reaction had a possible dose response relationship: fatigue (incidences were placebo, 0%; 5 mg, 3.8%; 10 mg, 22.0%; 15 mg, 18.5%).

Tourette's Disorder

In a study of pediatric patients (7 to 17 years of age) with Tourette's disorder, no common adverse reaction(s) had a dose response relationship.

Extrapyramidal Symptoms

Schizophrenia

In short-term, placebo-controlled trials in schizophrenia in adults, the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 13% vs. 12% for placebo; and the incidence of akathisia-related events for ABILIFY-treated patients was 8% vs. 4% for placebo. In the short-term, placebo-controlled trial of schizophrenia in pediatric patients (13 to 17 years), the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 25% vs. 7% for placebo; and the incidence of akathisia-related events for ABILIFY-treated patients was 9% vs. 6% for placebo.

Objectively collected data from those trials was collected on the Simpson Angus Rating Scale (for EPS), the Barnes Akathisia Scale (for akathisia), and the Assessments of Involuntary Movement Scales (for dyskinesias). In the adult schizophrenia trials, the objectively collected data did not show a difference between ABILIFY and placebo, with the exception of the Barnes Akathisia Scale (ABILIFY, 0.08; placebo, -0.05). In the pediatric (13 to 17 years) schizophrenia trial, the objectively collected data did not show a difference between ABILIFY and placebo, with the exception of the Simpson Angus Rating Scale (ABILIFY, 0.24; placebo, -0.29).

Similarly, in a long-term (26-week), placebo-controlled trial of schizophrenia in adults, objectively collected data on the Simpson Angus Rating Scale (for EPS), the Barnes Akathisia Scale (for akathisia), and the Assessments of Involuntary Movement Scales (for dyskinesias) did not show a difference between ABILIFY and placebo.

Bipolar Mania

In the short-term, placebo-controlled trials in bipolar mania in adults, the incidence of reported EPS-related events, excluding events related to akathisia, for monotherapy ABILIFY-treated patients was 16% vs. 8% for placebo and the incidence of akathisia-related events for monotherapy ABILIFY-treated patients was 13% vs. 4% for placebo. In the 6-week, placebo-controlled trial in bipolar mania for adjunctive therapy with lithium or valproate, the incidence of reported EPS-related events, excluding events related to akathisia for adjunctive ABILIFY-treated patients was 15% vs. 8% for adjunctive placebo and the incidence of akathisia-related events for adjunctive ABILIFY-treated patients was 19% vs. 5% for adjunctive placebo. In the short-term, placebo-controlled trial in bipolar mania in pediatric (10 to 17 years) patients, the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 26% vs. 5% for placebo and the incidence of akathisia-related events for ABILIFY-treated patients was 10% vs. 2% for placebo.

In the adult bipolar mania trials with monotherapy ABILIFY, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between ABILIFY and placebo (ABILIFY, 0.50; placebo, -0.01 and ABILIFY, 0.21; placebo, -0.05). Changes in the Assessments of Involuntary Movement Scales were similar for the ABILIFY and placebo groups. In the bipolar mania trials with ABILIFY as adjunctive therapy with either lithium or valproate, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between adjunctive ABILIFY and adjunctive placebo (ABILIFY, 0.73; placebo, 0.07 and ABILIFY, 0.30; placebo, 0.11). Changes in the Assessments of Involuntary Movement Scales were similar for adjunctive ABILIFY and adjunctive placebo. In the pediatric (10 to 17 years), short-term, bipolar mania trial, the Simpson Angus Rating Scale showed a significant difference between ABILIFY and placebo (ABILIFY, 0.90; placebo, -0.05). Changes in the Barnes Akathisia Scale and the Assessments of Involuntary Movement Scales were similar for the ABILIFY and placebo groups.

Major Depressive Disorder

In the short-term, placebo-controlled trials in major depressive disorder, the incidence of reported EPS-related events, excluding events related to akathisia, for adjunctive ABILIFY-treated patients was 8% vs. 5% for adjunctive placebo-treated patients; and the incidence of akathisia-related events for adjunctive ABILIFY-treated patients was 25% vs. 4% for adjunctive placebo-treated patients.

In the major depressive disorder trials, the Simpson Angus Rating Scale and the Barnes Akathisia Scale showed a significant difference between adjunctive ABILIFY and adjunctive placebo (ABILIFY, 0.31; placebo, 0.03 and ABILIFY, 0.22; placebo, 0.02). Changes in the Assessments of Involuntary Movement Scales were similar for the adjunctive ABILIFY and adjunctive placebo groups.

Autistic Disorder

In the short-term, placebo-controlled trials in autistic disorder in pediatric patients (6 to 17 years), the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 18% vs. 2% for placebo and the incidence of akathisia-related events for ABILIFY-treated patients was 3% vs. 9% for placebo.

In the pediatric (6 to 17 years) short-term autistic disorder trials, the Simpson Angus Rating Scale showed a significant difference between ABILIFY and placebo (ABILIFY, 0.1; placebo, 0.4). Changes in the Barnes Akathisia Scale and the Assessments of Involuntary Movement Scales were similar for the ABILIFY and placebo groups.

Tourette's Disorder

In the short-term, placebo-controlled trials in Tourette's disorder in pediatric patients (6 to 18 years), the incidence of reported EPS-related events, excluding events related to akathisia, for ABILIFY-treated patients was 7% vs. 6% for placebo and the incidence of akathisia-related events for ABILIFY-treated patients was 4% vs. 6% for placebo.

In the pediatric (6 to 18 years) short-term Tourette's disorder trials, changes in the Simpson Angus Rating Scale, Barnes Akathisia Scale and Assessments of Involuntary Movement Scale were not clinically meaningfully different for ABILIFY and placebo.

Agitation Associated with Schizophrenia or Bipolar Mania

In the placebo-controlled trials in patients with agitation associated with schizophrenia or bipolar mania, the incidence of reported EPS-related events excluding events related to akathisia for ABILIFY-treated patients was 2% vs. 2% for placebo and the incidence of akathisia-related events for ABILIFY-treated patients was 2% vs. 0% for placebo. Objectively collected data on the Simpson Angus Rating Scale (for EPS) and the Barnes Akathisia Scale (for akathisia) for all treatment groups did not show a difference between ABILIFY and placebo.

Dystonia

Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Additional Findings Observed In Clinical Trials

Adverse Reactions in Long-Term, Double-Blind, Placebo-Controlled Trials

The adverse reactions reported in a 26-week, double-blind trial comparing oral ABILIFY and placebo in patients with schizophrenia were generally consistent with those reported in the short-term, placebo-controlled trials, except for a higher incidence of tremor [8% (12/153) for ABILIFY vs. 2% (3/153) for placebo]. In this study, the majority of the cases of tremor were of mild intensity (8/12 mild and 4/12 moderate), occurred early in therapy (9/12 ≤ 49 days), and were of limited duration (7/12 ≤ 10 days). Tremor infrequently led to discontinuation ( < 1%) of ABILIFY. In addition, in a long-term (52 week), active-controlled study, the incidence of tremor was 5% (40/859) for ABILIFY. A similar profile was observed in a long-term monotherapy study and a long-term adjunctive study with lithium and valproate in bipolar disorder.

Other Adverse Reactions Observed During the Premarketing Evaluation Of ABILIFY

The following listing does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, 4) which were not considered to have significant clinical implications, or 5) which occurred at a rate equal to or less than placebo.

Reactions are categorized by body system according to the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients:

Adults -Oral Administration

Blood and Lymphatic System Disorders: rare -thrombocytopenia

Cardiac Disorders: infrequent - bradycardia, palpitations, rare - atrial flutter, cardiorespiratory arrest, atrioventricular block, atrial fibrillation, angina pectoris, myocardial ischemia, myocardial infarction, cardiopulmonary failure

Eye Disorders: infrequent - photophobia; rare -diplopia

Gastrointestinal Disorders: infrequent -gastroesophageal reflux disease

General Disorders and Administration Site Conditions: frequent -asthenia; infrequent - peripheral edema, chest pain; rare - face edema

Hepatobiliary Disorders: rare -hepatitis, jaundice

Immune System Disorders: rare -hypersensitivity

Injury, Poisoning, and Procedural Complications: infrequent fall; rare heat stroke

Investigations: frequent -weight decreased, infrequent -hepatic enzyme increased, blood glucose increased, blood lactate dehydrogenase increased, gamma glutamyl transferase increased; rare - blood prolactin increased, blood urea increased, blood creatinine increased, blood bilirubin increased, electrocardiogram QT prolonged, glycosylated hemoglobin increased

Metabolism and Nutrition Disorders: frequent - anorexia; infrequent -rare - hypokalemia, hyponatremia, hypoglycemia

Musculoskeletal and Connective Tissue Disorders: infrequent -muscular weakness, muscle tightness; rare - rhabdomyolysis, mobility decreased

Nervous System Disorders: infrequent -parkinsonism, memory impairment, cogwheel rigidity, hypokinesia, myoclonus, bradykinesia; rare akinesia, myoclonus, coordination abnormal, speech disorder, Grand Mal convulsion; < 1/10,000 patients -choreoathetosis

Psychiatric Disorders: infrequent - aggression, loss of libido, delirium; rare - libido increased, anorgasmia, tic, homicidal ideation, catatonia, sleep walking

Renal and Urinary Disorders: rare -urinary retention, nocturia

Reproductive System and Breast Disorders: infrequent -erectile dysfunction; rare - gynaecomastia, menstruation irregular, amenorrhea, breast pain, priapism

Respiratory, Thoracic, and Mediastinal Disorders: infrequent -nasal congestion, dyspnea

Skin and Subcutaneous Tissue Disorders: infrequent -rash, hyperhidrosis, pruritus, photosensitivity reaction, alopecia; rare -urticaria

Vascular Disorders: infrequent hypotension, hypertension

Pediatric Patients -Oral Administration

Most adverse events observed in the pooled database of 1,686 pediatric patients, aged 6 to 18 years, were also observed in the adult population. Additional adverse reactions observed in the pediatric population are listed below.

Eye Disorders :infrequent -oculogyric crisis

Gastrointestinal Disorders: infrequent -tongue dry, tongue spasm

Investigations: frequent -blood insulin increased

Nervous System Disorders: infrequent -sleep talking

Renal and Urinary Disorders frequent - enuresis

Skin and Subcutaneous Tissue Disorders: infrequent -hirsutism

Adults -Intramuscular Injection

Most adverse reactions observed in the pooled database of 749 adult patients treated with ABILIFY injection, were also observed in the adult population treated with oral ABILIFY. Additional adverse reactions observed in the ABILIFY injection population are listed below.

General Disorders and Administration Site Conditions: ≥ 1/100 patients -injection site reaction; ≥ 1/1000 patients and < 1/100 patients -venipuncture site bruise

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ABILIFY. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to establish a causal relationship to drug exposure: occurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups and blood glucose fluctuation.

Clinical pharmacology

Mechanism Of Action

The mechanism of action of aripiprazole in schizophrenia or bipolar mania, is unknown. However, the efficacy of aripiprazole could be mediated through a combination of partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Actions at receptors other than D2, 5HT1A, and 5-HT2A may explain some of the other clinical effects of aripiprazole (e.g., the orthostatic hypotension observed with aripiprazole may be explained by its antagonist activity at adrenergic alpha1 receptors).

Pharmacodynamics

Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors (Ki values of 0.34 nM, 0.8 nM, 1.7 nM, and 3.4 nM, respectively), moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors (Ki values of 44 nM, 15 nM, 39 nM, 57 nM, and 61 nM, respectively), and moderate affinity for the serotonin reuptake site (Ki=98 nM). Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50 > 1000 nM). [Aripiprazole functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptor.]

Pharmacokinetics

ABILIFY activity is presumably primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole, which has been shown to have affinities for D2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma. The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydroaripiprazole, respectively. Steady-state concentrations are attained within 14 days of dosing for both active moieties. Aripiprazole accumulation is predictable from single-dose pharmacokinetics. At steady-state, the pharmacokinetics of aripiprazole is dose-proportional. Elimination of aripiprazole is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP3A4. For CYP2D6 poor metabolizers, the mean elimination half-life for aripiprazole is about 146 hours.

Pharmacokinetic studies showed that ABILIFY DISCMELT Orally Disintegrating Tablets are bioequivalent to ABILIFY Tablets.

Oral Administration Absorption

Tablet: Aripiprazole is well absorbed after administration of the tablet, with peak plasma concentrations occurring within 3 hours to 5 hours; the absolute oral bioavailability of the tablet formulation is 87%. ABILIFY can be administered with or without food. Administration of a 15 mg ABILIFY Tablet with a standard high-fat meal did not significantly affect the Cmax or AUC of aripiprazole or its active metabolite, dehydro-aripiprazole, but delayed Tmax by 3 hours for aripiprazole and 12 hours for dehydro-aripiprazole.

Oral Solution: Aripiprazole is well absorbed when administered orally as the solution. At equivalent doses, the plasma concentrations of aripiprazole from the solution were higher than that from the tablet formulation. In a relative bioavailability study comparing the pharmacokinetics of 30 mg aripiprazole as the oral solution to 30 mg aripiprazole tablets in healthy subjects, the solution to tablet ratios of geometric mean Cmax and AUC values were 122% and 114%, respectively [see DOSAGE AND ADMINISTRATION]. The single-dose pharmacokinetics of aripiprazole were linear and dose-proportional between the doses of 5 mg to 30 mg.

Distribution

The steady-state volume of distribution of aripiprazole following intravenous administration is high (404 L or 4.9 L/kg), indicating extensive extravascular distribution. At therapeutic concentrations, aripiprazole and its major metabolite are greater than 99% bound to serum proteins, primarily to albumin. In healthy human volunteers administered 0.5 to 30 mg/day aripiprazole for 14 days, there was dose-dependent D2 receptor occupancy indicating brain penetration of aripiprazole in humans.

Metabolism And Elimination

Aripiprazole is metabolized primarily by three biotransformation pathways: dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP3A4. Aripiprazole is the predominant drug moiety in the systemic circulation. At steady-state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma.

Following a single oral dose of [14C]-labeled aripiprazole, approximately 25% and 55% of the administered radioactivity was recovered in the urine and feces, respectively. Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces.

Drug Interaction Studies

Effects of other drugs on the exposures of aripiprazole and dehydro-aripiprazole are summarized in Figure 1 and Figure 2, respectively. Based on simulation, a 4.5-fold increase in mean Cmax and AUC values at steady-state is expected when extensive metabolizers of CYP2D6 are administered with both strong CYP2D6 and CYP3A4 inhibitors. A 3-fold increase in mean Cmax and AUC values at steady-state is expected in poor metabolizers of CYP2D6 administered with strong CYP3A4 inhibitors.

Figure 1: The effects of other drugs on aripiprazole pharmacokinetics

Figure 2: The effects of other drugs on dehydro-aripiprazole pharmacokinetics

The effects of ABILIFY on the exposures of other drugs are summarized in Figure 3. A population PK analysis in patients with major depressive disorder showed no substantial change in plasma concentrations of fluoxetine (20 or 40 mg/day), paroxetine CR (37.5 or 50 mg/day), or sertraline (100 or 150 mg/day) dosed to steady-state. The steady-state plasma concentrations of fluoxetine and norfluoxetine increased by about 18% and 36%, respectively, and concentrations of paroxetine decreased by about 27%. The steady-state plasma concentrations of sertraline and desmethylsertraline were not substantially changed when these antidepressant therapies were coadministered with aripiprazole.

Figure 3: The effects of ABILIFY on pharmacokinetics of other drugs

Studies In Specific Populations

Exposures of aripiprazole and dehydro-aripiprazole in specific populations are summarized in Figure 4 and Figure 5, respectively. In addition, in pediatric patients (10 to 17 years of age) administered with Abilify (20 mg to 30 mg), the body weight corrected aripiprazole clearance was similar to the adults.

Figure 4: Effects of intrinsic factors on aripiprazole pharmacokinetics

Figure 5: Effects of intrinsic factors on dehydro-aripiprazole pharmacokinetics

Intramuscular Administration

In two pharmacokinetic studies of aripiprazole injection administered intramuscularly to healthy subjects, the median times to the peak plasma concentrations were at 1 hour and 3 hours. A 5 mg intramuscular injection of aripiprazole had an absolute bioavailability of 100%. The geometric mean maximum concentration achieved after an intramuscular dose was on average 19% higher than the Cmax of the oral tablet. While the systemic exposure over 24 hours was generally similar between aripiprazole injection given intramuscularly and after oral tablet administration, the aripiprazole AUC in the first 2 hours after an intramuscular injection was 90% greater than the AUC after the same dose as a tablet. In stable patients with schizophrenia or schizoaffective disorder, the pharmacokinetics of aripiprazole after intramuscular administration were linear over a dose range of 1 mg to 45 mg. Although the metabolism of aripiprazole injection was not systematically evaluated, the intramuscular route of administration would not be expected to alter the metabolic pathways.

Animal Toxicology And/Or Pharmacology

Aripiprazole produced retinal degeneration in albino rats in a 26-week chronic toxicity study at a dose of 60 mg/kg and in a 2-year carcinogenicity study at doses of 40 and 60 mg/kg. The 40 and 60 mg/kg/day doses are 13 and 19 times the maximum recommended human dose (MRHD) based on mg/m²and 7 to 14 times human exposure at MRHD based on AUC. Evaluation of the retinas of albino mice and of monkeys did not reveal evidence of retinal degeneration. Additional studies to further evaluate the mechanism have not been performed. The relevance of this finding to human risk is unknown.

Clinical Studies

Efficacy of the oral formulations of ABILIFY (aripiprazole) was established in the following adequate and well-controlled trials:

  • Four short-term trials and one maintenance trial in adult patients and one short-term trial in adolescents (ages 13-17) with schizophrenia [see Clinical Studies]
  • Four short-term monotherapy trials and one 6-week adjunctive trial in adult patients and one short-term monotherapy trial in pediatric patients (ages 1017) with manic or mixed episodes [see Clinical Studies]
  • One maintenance monotherapy trial and in one maintenance adjunctive trial in adult patients with bipolar I disorder [see Clinical Studies]
  • Two short-term trials in adult patients with MDD who had an inadequate response to antidepressant therapy during the current episode [see Clinical Studies]
  • Two short-term trials in pediatric patients (ages 6-17 years) for the treatment of irritability associated with autistic disorder [see Clinical Studies]
  • Two short-term trials in pediatric patients (ages 6-18 years) with Tourette's disorder [see Clinical Studies]

Efficacy of the injectable formulation of ABILIFY (aripiprazole) was established in the following adequate and well-controlled trials:

  • Three 24-hour trials in agitated adult patients with schizophrenia or manic/mixed episodes of bipolar I disorder [see Clinical Studies]

Schizophrenia

Adults

The efficacy of ABILIFY in the treatment of schizophrenia was evaluated in five short-term (4-week and 6-week), placebo-controlled trials of acutely relapsed inpatients who predominantly met DSM-III/IV criteria for schizophrenia. Four of the five trials were able to distinguish ABILIFY from placebo, but one study, the smallest, did not. Three of these studies also included an active control group consisting of either risperidone (one trial) or haloperidol (two trials), but they were not designed to allow for a comparison of ABILIFY and the active comparators.

In the four positive trials for ABILIFY, four primary measures were used for assessing psychiatric signs and symptoms. Efficacy was evaluated using the total score on the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30 item scale that measures positive symptoms of schizophrenia (7 items), negative symptoms of schizophrenia (7 items), and general psychopathology (16 items), each rated on a scale of 1 (absent) to 7 (extreme); total PANSS scores range from 30 to 210. The Clinical Global Impression (CGI) assessment reflects the impression of a skilled observer, fully familiar with the manifestations of schizophrenia, about the overall clinical state of the patient.

In a 4-week trial (n=414) comparing two fixed doses of ABILIFY (15 or 30 mg/day) to placebo, both doses of ABILIFY were superior to placebo in the PANSS total score (Study 1 in Table 26), PANSS positive subscale, and CGI-severity score. In addition, the 15 mg dose was superior to placebo in the PANSS negative subscale.

In a 4-week trial (n=404) comparing two fixed doses of ABILIFY (20 or 30 mg/day) to placebo, both doses of ABILIFY were superior to placebo in the PANSS total score (Study 2 in Table 26), PANSS positive subscale, PANSS negative subscale, and CGI-severity score.

In a 6-week trial (n=420) comparing three fixed doses of ABILIFY (10, 15, or 20 mg/day) to placebo, all three doses of ABILIFY were superior to placebo in the PANSS total score (Study 3 in Table 26), PANSS positive subscale, and the PANSS negative subscale.

In a 6-week trial (n=367) comparing three fixed doses of ABILIFY (2, 5, or 10 mg/day) to placebo, the 10 mg dose of ABILIFY was superior to placebo in the PANSS total score (Study 4 in Table 26), the primary outcome measure of the study. The 2 and 5 mg doses did not demonstrate superiority to placebo on the primary outcome measure.

Thus, the efficacy of 10, 15, 20, and 30 mg daily doses was established in two studies for each dose. Among these doses, there was no evidence that the higher dose groups offered any advantage over the lowest dose group of these studies.

An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age, gender, or race.

A longer-term trial enrolled 310 inpatients or outpatients meeting DSM-IV criteria for schizophrenia who were, by history, symptomatically stable on other antipsychotic medications for periods of 3 months or longer. These patients were discontinued from their antipsychotic medications and randomized to ABILIFY 15 mg/day or placebo for up to 26 weeks of observation for relapse. Relapse during the double-blind phase was defined as CGI-Improvement score of ≥ 5 (minimally worse), scores ≥ 5 (moderately severe) on the hostility or uncooperativeness items of the PANSS, or ≥ 20% increase in the PANSS total score. Patients receiving ABILIFY 15 mg/day experienced a significantly longer time to relapse over the subsequent 26 weeks compared to those receiving placebo (Study 5 in Figure 6).

Pediatric Patients

The efficacy of ABILIFY (aripiprazole) in the treatment of schizophrenia in pediatric patients (13 to 17 years of age) was evaluated in one 6-week, placebo-controlled trial of outpatients who met DSM-IV criteria for schizophrenia and had a PANSS score ≥ 70 at baseline. In this trial (n=302) comparing two fixed doses of ABILIFY (10 or 30 mg/day) to placebo, ABILIFY was titrated starting from 2 mg/day to the target dose in 5 days in the 10 mg/day treatment arm and in 11 days in the 30 mg/day treatment arm. Both doses of ABILIFY were superior to placebo in the PANSS total score (Study 6 in Table 26), the primary outcome measure of the study. The 30 mg/day dosage was not shown to be more efficacious than the 10 mg/day dose. Although maintenance efficacy in pediatric patients has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients.

Table 26: Schizophrenia Studies

Study Number Treatment Group Primary Efficacy Measure: PANSS
Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Differencea (95% CI)
Study 1 ABILIFY (15 mg/day)* 98.5 (17.2) -15.5 (2.40) -12.6 (-18.9, -6.2)
ABILIFY (30 mg/day)* 99.0 (19.2) -11.4 (2.39) -8.5 (-14.8, -2.1)
Placebo 100.2 (16.5) -2.9 (2.36) --
Study 2 ABILIFY (20 mg/day)* 92.6 (19.5) -14.5 (2.23) -9.6 (-15.4, -3.8)
ABILIFY (30 mg/day)* 94.2 (18.5) -13.9 (2.24) -9.0 (-14.8, -3.1)
Placebo 94.3 (18.5) -5.0 (2.17) --
Study 3 ABILIFY (10 mg/day)* 92.7 (19.5) -15.0 (2.38) -12.7 (-19.00, -6.41)
ABILIFY (15 mg/day)* 93.2 (21.6) -11.7 (2.38) -9.4 (-15.71, -3.08)
ABILIFY (20 mg/day)* 92.5 (20.9) -14.4 (2.45) -12.1 (-18.53, -5.68)
Placebo 92.3 (21.8) -2.3 (2.35) --
Study 4 ABILIFY (2 mg/day) 90.7 (14.5) -8.2 (1.90) -2.9 (-8.29, 2.47)
ABILIFY (5 mg/day) 92.0 (12.6) -10.6 (1.93) -5.2 (-10.7, 0.19)
ABILIFY (10 mg/day)* 90.0 (11.9) -11.3 (1.88) -5.9 (-11.3, -0.58)
Placebo 90.8 (13.3) -5.3 (1.97) --
Study 6 (Pediatric,13-17 years) ABILIFY (10 mg/day)* 93.6 (15.7) -26.7 (1.91) -5.5 (-10.7, -0.21)
ABILIFY (30 mg/day)* 94.0 (16.1) -28.6 (1.92) -7.4 (-12.7, -2.13)
Placebo 94.6 (15.6) -21.2 (1.93) --
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.
a Difference (drug minus placebo) in least-squares mean change from baseline.
* Doses statistically significantly superior to placebo.

Figure 6: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse (Schizophrenia Study 5)

Bipolar Disorder

Acute Treatment of Manic and Mixed Episodes

Adults

Monotherapy

The efficacy of ABILIFY as monotherapy in the acute treatment of manic episodes was established in four 3-week, placebo-controlled trials in hospitalized patients who met the DSM-IV criteria for bipolar I disorder with manic or mixed episodes. These studies included patients with or without psychotic features and two of the studies also included patients with or without a rapid-cycling course.

The primary instrument used for assessing manic symptoms was the Young Mania Rating Scale (Y-MRS), an 11-item clinician-rated scale traditionally used to assess the degree of manic symptomatology in a range from 0 (no manic features) to 60 (maximum score). A key secondary instrument included the Clinical Global Impression-Bipolar (CGI-BP) Scale.

In the four positive, 3-week, placebo-controlled trials (n=268; n=248; n=480; n=485) which evaluated ABILIFY in a range of 15 mg to 30 mg, once daily (with a starting dose of 30 mg/day in two studies and 15 mg/day in two studies), ABILIFY was superior to placebo in the reduction of Y-MRS total score (Studies 1-4 in Table 27) and CGI-BP Severity of Illness score (mania). In the two studies with a starting dose of 15 mg/day, 48% and 44% of patients were on 15 mg/day at endpoint. In the two studies with a starting dose of 30 mg/day, 86% and 85% of patients were on 30 mg/day at endpoint.

Adjunctive Therapy

The efficacy of adjunctive ABILIFY with concomitant lithium or valproate in the treatment of manic or mixed episodes was established in a 6-week, placebo-controlled study (n=384) with a 2-week lead-in mood stabilizer monotherapy phase in adult patients who met DSM-IV criteria for bipolar I disorder. This study included patients with manic or mixed episodes and with or without psychotic features.

Patients were initiated on open-label lithium (0.6 to 1.0 mEq/L) or valproate (50 to 125 μg/mL) at therapeutic serum levels, and remained on stable doses for 2 weeks. At the end of 2 weeks, patients demonstrating inadequate response (YMRS total score ≥ 16 and ≤ 25% improvement on the Y-MRS total score) to lithium or valproate were randomized to receive either ABILIFY (15 mg/day or an increase to 30 mg/day as early as day 7) or placebo as adjunctive therapy with open-label lithium or valproate. In the 6-week, placebo-controlled phase, adjunctive ABILIFY starting at 15 mg/day with concomitant lithium or valproate (in a therapeutic range of 0.6 to 1.0 mEq/L or 50 to 125 μg/mL, respectively) was superior to lithium or valproate with adjunctive placebo in the reduction of the Y-MRS total score (Study 5 in Table 27) and CGI-BP Severity of Illness score (mania). Seventy-one percent of the patients coadministered valproate and 62% of the patients coadministered lithium were on 15 mg/day at 6-week endpoint.

Pediatric Patients

The efficacy of ABILIFY in the treatment of bipolar I disorder in pediatric patients (10 to 17 years of age) was evaluated in one 4-week, placebo-controlled trial (n=296) of outpatients who met DSM-IV criteria for bipolar I disorder manic or mixed episodes with or without psychotic features and had a Y-MRS score ≥ 20 at baseline. This double-blind, placebo-controlled trial compared two fixed doses of ABILIFY (10 or 30 mg/day) to placebo. The ABILIFY dose was started at 2 mg/day, which was titrated to 5 mg/day after 2 days, and to the target dose in 5 days in the 10 mg/day treatment arm, and in 13 days in the 30 mg/day treatment arm. Both doses of ABILIFY were superior to placebo in change from baseline to week 4 on the Y-MRS total score (Study 6 in Table 27).

Table 27: Bipolar Studies

Study Number Treatment Group Primary Efficacy Measure: Y-MRS
Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Differencea (95% CI)
Study 1 ABILIFY (30 / 15 mg/day)* 29.0 (5.9) -12.52 (1.05) -5.33 (-7.90, -2.76)
Placebo 28.5 (4.6) -7.19 (1.07) --
Study 2 ABILIFY (30 / 15 mg/day)* 27.8 (5.7) -8.15 (1.23) -4.80 (-7.80, -1.80)
Placebo 29.1 (6.9) -3.35(1.22) --
Study 3 ABILIFY (15 - 30 mg/day)* 28.5 (5.6) -12.64 (0.84) -3.63 (-5.75 , -1.51)
Placebo 28.9 (5.9) 9.01 (0.81) --
Study 4 ABILIFY (15 -30 mg/day)* 28.0 (5.8) -11.98 (0.80) -2.28 (-4.44 , -0.11)
Placebo 28.3 (5.8) -9.70 (0.83) --
Study 5 ABILIFY (15 or 30 mg/day)* + 23.2 (5.7) -13.31 (0.50) -2.62 (-4.29 , -0.95)
Lithium/Valproate Placebo + Lithium/Valproate 23.0 (4.9) -10.70 (0.69) --
Study 6 (Pediatric,10-17 years) ABILIFY (10 mg/day)* 29.8 (6.5) -14.2 (0.89) -5.99 (-8.49, -3.50)
ABILIFY (30 mg/day)* 29.5 (6.3) -16.5 (0.87) -8.26 (-10.7, -5.77)
Placebo 30.7 (6.8) -8.2 (0.91) --
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.
a Difference (drug minus placebo) in least-squares mean change from baseline.
* Doses statistically significantly superior to placebo.

Maintenance Treatment Of Bipolar I Disorder

Monotherapy Maintenance Therapy

A maintenance trial was conducted in adult patients meeting DSM-IV criteria for bipolar I disorder with a recent manic or mixed episode who had been stabilized on open-label ABILIFY and who had maintained a clinical response for at least 6 weeks. The first phase of this trial was an open-label stabilization period in which inpatients and outpatients were clinically stabilized and then maintained on open-label ABILIFY (15 or 30 mg/day, with a starting dose of 30 mg/day) for at least 6 consecutive weeks. One hundred sixty-one outpatients were then randomized in a double-blind fashion, to either the same dose of ABILIFY they were on at the end of the stabilization and maintenance period or placebo and were then monitored for manic or depressive relapse. During the randomization phase, ABILIFY was superior to placebo on time to the number of combined affective relapses (manic plus depressive), the primary outcome measure for this study (Study 7 in Figure 7). A total of 55 mood events were observed during the double-blind treatment phase. Nineteen were from the ABILIFY group and 36 were from the placebo group. The number of observed manic episodes in the ABILIFY group (6) were fewer than that in the placebo group (19), while the number of depressive episodes in the ABILIFY group (9) was similar to that in the placebo group (11).

An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender; however, there were insufficient numbers of patients in each of the ethnic groups to adequately assess inter-group differences.

Figure 7: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse (Bipolar Study 7)

Adjunctive Maintenance Therapy

An adjunctive maintenance trial was conducted in adult patients meeting DSMIV criteria for bipolar I disorder with a recent manic or mixed episode. Patients were initiated on open-label lithium (0.6 to 1.0 mEq/L) or valproate (50 to 125 μg/mL) at therapeutic serum levels, and remained on stable doses for 2 weeks. At the end of 2 weeks, patients demonstrating inadequate response (Y-MRS total score ≥ 16 and ≤ 35% improvement on the Y-MRS total score) to lithium or valproate received ABILIFY with a starting dose of 15 mg/day with the option to increase to 30 mg or reduce to 10 mg as early as day 4, as adjunctive therapy with open-label lithium or valproate. Prior to randomization, patients on the combination of single-blind ABILIFY and lithium or valproate were required to maintain stability (Y-MRS and MADRS total scores ≤ 12) for 12 consecutive weeks. Three hundred thirty-seven patients were then randomized in a double-blind fashion, to either the same dose of ABILIFY they were on at the end of the stabilization period or placebo plus lithium or valproate and were then monitored for manic, mixed, or depressive relapse for a maximum of 52 weeks. ABILIFY was superior to placebo on the primary endpoint, time from randomization to relapse to any mood event (Study 8 in Figure 8). A mood event was defined as hospitalization for a manic, mixed, or depressive episode, study discontinuation due to lack of efficacy accompanied by Y-MRS score > 16 and/or a MADRS > 16, or an SAE of worsening disease accompanied by YMRS score > 16 and/or a MADRS > 16. A total of 68 mood events were observed during the double-blind treatment phase. Twenty-five were from the ABILIFY group and 43 were from the placebo group. The number of observed manic episodes in the ABILIFY group (7) were fewer than that in the placebo group (19), while the number of depressive episodes in the ABILIFY group (14) was similar to that in the placebo group (18). The Kaplan-Meier curves of the time from randomization to relapse to any mood event during the 52-week, double-blind treatment phase for ABILIFY and placebo groups are shown in Figure 8.

Figure 8: Kaplan-Meier Estimation of Cumulative Proportion of Patients with Relapse to Any Mood Event (Bipolar Study 8)

An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender; however, there were insufficient numbers of patients in each of the ethnic groups to adequately assess inter-group differences.

Adjunctive Treatment Of Major Depressive Disorder

Adults

The efficacy of ABILIFY in the adjunctive treatment of major depressive disorder (MDD) was demonstrated in two short-term (6-week), placebo-controlled trials of adult patients meeting DSM-IV criteria for MDD who had had an inadequate response to prior antidepressant therapy (1 to 3 courses) in the current episode and who had also demonstrated an inadequate response to 8 weeks of prospective antidepressant therapy (paroxetine controlled-release, venlafaxine extended-release, fluoxetine, escitalopram, or sertraline). Inadequate response for prospective treatment was defined as less than 50% improvement on the 17-item version of the Hamilton Depression Rating Scale (HAMD17), minimal HAMD17 score of 14, and a Clinical Global Impressions Improvement rating of no better than minimal improvement. Inadequate response to prior treatment was defined as less than 50% improvement as perceived by the patient after a minimum of 6 weeks of antidepressant therapy at or above the minimal effective dose.

The primary instrument used for assessing depressive symptoms was the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-rated scale used to assess the degree of depressive symptomatology. The key secondary instrument was the Sheehan Disability Scale (SDS), a 3-item self-rated instrument used to assess the impact of depression on three domains of functioning with each item scored from 0 (not at all) to 10 (extreme).

In the two trials (n=381, n=362), ABILIFY was superior to placebo in reducing mean MADRS total scores (Studies 1, 2 in Table 28). In one study, ABILIFY was also superior to placebo in reducing the mean SDS score.

In both trials, patients received ABILIFY adjunctive to antidepressants at a dose of 5 mg/day. Based on tolerability and efficacy, doses could be adjusted by 5 mg increments, one week apart. Allowable doses were: 2, 5, 10, 15 mg/day, and for patients who were not on potent CYP2D6 inhibitors fluoxetine and paroxetine, 20 mg/day. The mean final dose at the end point for the two trials was 10.7 and 11.4 mg/day.

An examination of population subgroups did not reveal evidence of differential response based on age, choice of prospective antidepressant, or race. With regard to gender, a smaller mean reduction on the MADRS total score was seen in males than in females.

Table 28: Adjunctive Treatment of Major Depressive Disorder Studies

Study Number Treatment Group Primary Efficacy Measure: MADRS
Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Differencea(95% CI)
Study 1 ABILIFY (5-20 mg/day)* + 25.2(6.2) -8.49 (0.66) -2.84 (-4.53 , -1.15)
Antidepressant Placebo + Antidepressant 27.0 (5.5) -5.65 (0.64) --
Study 2 ABILIFY (5-20 mg/day)* + 26.0 (6.0) -8.78 (0.63) -3.01 (-4.66 , -1.37)
Antidepressant Placebo + Antidepressant 26.0 (6.5) -5.77 (0.67) --
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.
a Difference (drug minus placebo) in least-squares mean change from baseline.
* Doses statistically significantly superior to placebo.

Irritability Associated With Autistic Disorder

Pediatric Patients

The efficacy of ABILIFY (aripiprazole) in the treatment of irritability associated with autistic disorder was established in two 8-week, placebo-controlled trials in pediatric patients (6 to 17 years of age) who met the DSM-IV criteria for autistic disorder and demonstrated behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these problems. Over 75% of these subjects were under 13 years of age.

Efficacy was evaluated using two assessment scales: the Aberrant Behavior Checklist (ABC) and the Clinical Global Impression-Improvement (CGI-I) scale. The primary outcome measure in both trials was the change from baseline to endpoint in the Irritability subscale of the ABC (ABC-I). The ABC-I subscale measured symptoms of irritability in autistic disorder.

The results of these trials are as follows:

In one of the 8-week, placebo-controlled trials, children and adolescents with autistic disorder (n=98), aged 6 to 17 years, received daily doses of placebo or ABILIFY 2 to 15 mg/day. ABILIFY, starting at 2 mg/day with increases allowed up to 15 mg/day based on clinical response, significantly improved scores on the ABC-I subscale and on the CGI-I scale compared with placebo. The mean daily dose of ABILIFY at the end of 8week treatment was 8.6 mg/day (Study 1 in Table 29).

In the other 8-week, placebo-controlled trial in children and adolescents with autistic disorder (n=218), aged 6 to 17 years, three fixed doses of ABILIFY (5 mg/day, 10 mg/day, or 15 mg/day) were compared to placebo. ABILIFY dosing started at 2 mg/day and was increased to 5 mg/day after one week. After a second week, it was increased to 10 mg/day for patients in the 10 and 15 mg dose arms, and after a third week, it was increased to 15 mg/day in the 15 mg/day treatment arm (Study 2 in Table 29). All three doses of ABILIFY significantly improved scores on the ABC-I subscale compared with placebo.

Table 29: Irritability Associated with Autistic Disorder Studies (Pediatric)

Study Number Treatment Group Primary Efficacy Measure: ABC-I
Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Differencea (95% CI)
Study 1 ABILIFY (2-15 mg/day)* 29.6 (6.37) -12.9 (1.44) -7.9 (-11.7, -4.1)
Placebo 30.2 (6.52) -5.0 (1.43) --
Study 2 ABILIFY (5 mg/day)* 28.6 (7.56) -12.4 (1.36) -4.0 (-7.7, -0.4)
ABILIFY (10 mg/day)* 28.2 (7.36) -13.2 (1.25) -4.8 (-8.4, -1.3)
ABILIFY (15 mg/day)* 28.9 (6.41) -14.4 (1.31) -6.0 (-9.6, -2.3)
Placebo 28.0 (6.89) -8.4 (1.39) --
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.
a Difference (drug minus placebo) in least-squares mean change from baseline.
* Doses statistically significantly superior to placebo.

Tourette's Disorder

Pediatric Patients

The efficacy of ABILIFY (aripiprazole) in the treatment of Tourette's disorder was established in one 8-week (7 to 17 years of age) and one 10-week (6 to 18 years of age), placebo-controlled trials in pediatric patients (6 to 18 years of age) who met the DSM-IV criteria for Tourette's disorder and had a Total Tic score (TTS) ≥ 20 -22 on the Yale Global Tic Severity Scale (YGTSS). The YGTSS is a fully validated scale designed to measure current tic severity.

Efficacy was evaluated using two assessment scales: 1) the Total Tic score (TTS) of the YGTSS and 2) the Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS), a clinician-determined summary measure that takes into account all available patient information. Over 65% of these patients were under 13 years of age.

The primary outcome measure in both trials was the change from baseline to endpoint in the TTS of the YGTSS. Ratings for the TTS are made along 5 different dimensions on a scale of 0 to 5 for motor and vocal tics each. Summation of these 10 scores provides a TTS (i.e., 0-50).

The results of these trials are as follows:

In the 8-week, placebo-controlled, fixed-dose trial, children and adolescents with Tourette's disorder (n=133), aged 7 to 17 years, were randomized 1:1:1 to low dose ABILIFY, high dose ABILIFY, or placebo. The target doses for the low and high dose ABILIFY groups were based on weight. Patients < 50 kg in the low dose ABILIFY group started at 2 mg per day with a target dose of 5 mg per day after 2 days. Patients ≥ 50 kg in the low dose ABILIFY group, started at 2 mg per day increased to 5 mg per day after 2 days, with a subsequent increase to a target dose of 10 mg per day at day 7. Patients < 50 kg in the high dose ABILIFY group started at 2 mg per day increased to 5 mg per day after 2 days, with a subsequent increase to a target dose of 10 mg per day at day 7. Patients ≥ 50 kg in the high dose ABILIFY group, started at 2 mg per day increased to 5 mg per day after 2 days, with a subsequent increase to a dose of 10 mg per day at day 7 and were allowed weekly increases of 5 mg per day up to a target dose 20 mg per day at Day 21. ABILIFY (both high and low dose groups) demonstrated statistically significantly improved scores on the YGTSS TTS (Study 1 in Table 30) and on the CGI-TS scale compared with placebo. The estimated improvements on the YGTSS TTS over the course of the study are displayed in Figure 9.

Figure 9: Least Square Means of Change from Baseline in YGTSS TTS by Week (Tourette's Disorder Study 1)

In the 10-week, placebo-controlled, flexible-dose trial in children and adolescents with Tourette's disorder (n=61), aged 6 to 18 years, patients received daily doses of placebo or ABILIFY, starting at 2 mg/day with increases allowed up to 20 mg/day based on clinical response. ABILIFY demonstrated statistically significantly improved scores on the YGTSS TTS scale compared with placebo (Study 2 in Table 30). The mean daily dose of ABILIFY at the end of 10-week treatment was 6.54 mg/day.

Table 30: Tourette's Disorder Studies (Pediatric)

Study Number Treatment Group Primary Efficacy Measure: YGTSS TTS
Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Differencea (95% CI)
Study 1 ABILIFY (low dose)* 29.2 (5.63) -13.4 (1.59) -6.3 (-10.2, -2.3)
ABILIFY (high dose)* 31.2 (6.40) -16.9 (1.61) -9.9 (-13.8, -5.9)
Placebo 30.7 (5.95) -7.1 (1.55) --
Study 2 ABILIFY (2-20 mg/day)* 28.3 (5.51) -15.0 (1.51) -5.3 (-9.8, -0.9)
Placebo 29.5 (5.60) -9.6 (1.64) --
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.
a Difference (drug minus placebo) in least-squares mean change from baseline.
* Doses statistically significantly superior to placebo.

Agitation Associated With Schizophrenia Or Bipolar Mania

The efficacy of intramuscular ABILIFY for injection for the treatment of agitation was established in three short-term (24-hour), placebo-controlled trials in agitated inpatients from two diagnostic groups: schizophrenia and bipolar I disorder (manic or mixed episodes, with or without psychotic features). Each of the trials included a single active comparator treatment arm of either haloperidol injection (schizophrenia studies) or lorazepam injection (bipolar mania study). Patients could receive up to three injections during the 24-hour treatment periods; however, patients could not receive the second injection until after the initial 2-hour period when the primary efficacy measure was assessed. Patients enrolled in the trials needed to be: (1) judged by the clinical investigators as clinically agitated and clinically appropriate candidates for treatment with intramuscular medication, and (2) exhibiting a level of agitation that met or exceeded a threshold score of ≥ 15 on the five items comprising the Positive and Negative Syndrome Scale (PANSS) Excited Component (i.e., poor impulse control, tension, hostility, uncooperativeness, and excitement items) with at least two individual item scores ≥ 4 using a 1-7 scoring system (1 = absent, 4 = moderate, 7 = extreme). In the studies, the mean baseline PANSS Excited Component score was 19, with scores ranging from 15 to 34 (out of a maximum score of 35), thus suggesting predominantly moderate levels of agitation with some patients experiencing mild or severe levels of agitation. The primary efficacy measure used for assessing agitation signs and symptoms in these trials was the change from baseline in the PANSS Excited Component at 2 hours post-injection. A key secondary measure was the Clinical Global Impression of Improvement (CGI-I) Scale. The results of the trials follow:

In a placebo-controlled trial in agitated inpatients predominantly meeting DSM-IV criteria for schizophrenia (n=350), four fixed ABILIFY injection doses of 1 mg, 5.25 mg, 9.75 mg, and 15 mg were evaluated. At 2 hours post-injection, the 5.25 mg, 9.75 mg, and 15 mg doses were statistically superior to placebo in the PANSS Excited Component (Study 1 in Table 31) and on the CGI-I Scale.

In a second placebo-controlled trial in agitated inpatients predominantly meeting DSM-IV criteria for schizophrenia (n=445), one fixed ABILIFY injection dose of 9.75 mg was evaluated. At 2 hours post-injection, ABILIFY for injection was statistically superior to placebo in the PANSS Excited Component (Study 2 in Table 31) and on the CGI-I Scale.

In a placebo-controlled trial in agitated inpatients meeting DSMIV criteria for bipolar I disorder (manic or mixed) (n=291), two fixed ABILIFY injection doses of 9.75 mg and 15 mg were evaluated. At 2 hours post-injection, both doses were statistically superior to placebo in the PANSS Excited Component (Study 3 in Table 31).

Examination of population subsets (age, race, and gender) did not reveal any differential responsiveness on the basis of these subgroupings.

Table 31: Agitation Associated with Schizophrenia or Bipolar Mania Studies

Study Number Treatment Group Primary Efficacy Measure: PANSS Excited Component
Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Differencea (95% CI)
Agitation Associated with Schizophrenia
Study 1 ABILIFY (1 mg) 19.16 (3.26) -4.47 (0.72) -1.19 (-2.96 , 0.59)
ABILIFY (5.25 mg)* 19.41 (3.31) -5.65 (0.68) -2.37 (-4.10 , -0.63)
ABILIFY (9.75 mg)* 19.42 (2.80) -6.69 (0.72) -3.40 (-5.18 , -1.62)
ABILIFY (15 mg)* 19.34 (2.38) -5.72 (0.72) -2.44 (-4.21 , -0.68)
Placebo 19.18 (2.95) -3.28 (0.70) --
Study 2 ABILIFY (9.75 mg)* 18.82 (2.67) -7.27 (0.59) -2.48 (-3.77, -1.19)
Placebo 18.74 (2.71) -4.78 (0.69) --
Agitation Associated with Bipolar Mania
Study 3 ABILIFY (9.75 mg)* 18.77 (2.45) -8.74 (0.57) -2.99 (-4.53, -1.44)
ABILIFY (15 mg)* 18.29 (2.49) -8.67 (0.57) -2.91 (-4.44, -1.38)
Placebo 17.95 (2.63) -5.76 (0.58) --
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval.
a Difference (drug minus placebo) in least-squares mean change from baseline.
* Doses statistically significantly superior to placebo.

Abilify Precautions

Oral/Injectable:

Serious side effects have been reported with Abilify including the following

  • neuroleptic malignant syndrome (NMS). Tell your healthcare provider right away if you have some or all of the following symptoms of this life-threatening nervous system disorder:
    • high fever
    • stiff muscles
    • confusion
    • sweating
    • changes in pulse, heart rate, and blood pressure
  • high blood sugar. Increases in blood sugar can happen in some people who take Abilify.
    Call your healthcare provider if you have any of these symptoms of high blood sugar while taking Abilify:
    • feel very thirsty
    • need to urinate more than usual
    • feel very hungry
    • feel weak or tired
    • feel sick to your stomach
    • feel confused, or your breath smells fruity
  • Increase in weight. Weight gain has been reported in patients taking medicines like Abilify, so you and your healthcare provider should check your weight regularly. For children and adolescent patients (6 to 17 years of age) weight gain should be compared against that expected with normal growth.
  • difficulty swallowing. This may lead to aspiration and choking.
  • tardive dyskinesia. Call your healthcare provider about any movements you cannot control in your face, tongue, or other body parts. These may be signs of a serious condition. Tardive dyskinesia may not go away, even if you stop taking Abilify. Tardive dyskinesia may also start after you stop taking Abilify.
  • orthostatic hypotension (decreased blood pressure). Lightheadedness or fainting can occur when rising too quickly from a sitting or lying position.
  • Low white blood cell count
  • Seizures (convulsions)
  • Problems controlling your body temperature so that you feel too warm. Avoid getting over-heated or dehydrated. Do not over-exercise. In hot weather, stay inside in a cool place if possible. Stay out of the sun. Do not wear too much or heavy clothing. Drink plenty of water while taking Abilify.

Important information about antidepressant medicines:

  • Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
  • Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
  • Antidepressant medicines have other side effects. Talk to the healthcare provider about the side effects of the medicine prescribed for you or your family member.
  • Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
  • Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child’s healthcare provider for more information.

Do not drive, operate heavy machinery, or do other dangerous activities until you know how Abilify affects you. Abilify may make you drowsy. Do not drink alcohol while taking Abilify.

Abilify Overdose

If you take too much Abilify call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Abilify is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.
 

Where can i get more information?

Your pharmacist can provide more information about aripiprazole.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Tips

  • May be administered with or without food.
  • Take only as directed by your doctor. Do not increase the dosage without your doctor's advice.
  • Abilify is available as oral tablets, orally-disintegrating tablets, and an oral solution. Disintegrating tablets should not be removed from their blister until ready to administer. Dry hands should be used to peel back the foil on the blister rather than attempting to pop the tablet through the foil. The tablet should then be placed on the tongue. May be taken with or without liquid, but do not attempt to split the tablet.
  • May cause sedation or impair judgment skills and affect your ability to drive or operate machinery. Avoid alcohol.
  • Avoid overheating and dehydration.
  • Seek urgent medical advice if you develop uncontrolled body movements, confusion, high fever, lightheadedness, fainting, seizures, have problems controlling your body temperature, or difficulty swallowing.
  • Talk to your doctor or pharmacist before buying other medications over the counter to check that they are compatible with Abilify.

Response and Effectiveness

  • Peak blood levels are reached within three to five hours of taking oral Abilify. Effects are long lasting, so Abilify is usually taken once daily.
  • May take up to two weeks to achieve stable blood concentrations.
  • Target dosages of 10-15mg per day of Abilify are recommended for schizophrenia; dosages above 15 mg/day have not been found to be more effective than 15 mg/day.
  • Dosage reductions may be needed for people known to be poor metabolizers of drugs like Abilify, or in people taking other medications known to interfere with the hepatic enzymes CYP2D6 and CYP3A4. Conversely, a dosage increase of Abilify may be needed when given with medications that induce CYP3A4.

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Aripiprazole Levels and Effects while Breastfeeding

Summary of Use during Lactation

Limited information indicates that maternal doses of aripiprazole up to 15 mg daily produce low levels in milk, but until more data become available, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.[1] Aripiprazole can lower serum prolactin in a dose-related manner and can affect the milk supply variably.

Drug Levels

Maternal Levels. A women who was 6 months postpartum was taking aripiprazole 15 mg by mouth daily. Milk levels after 11 and 12 days of therapy (times not stated) at that dose were 13 and 14 mcg/L.[2]

A woman took aripiprazole 15 mg daily by mouth during pregnancy and postpartum. At 3 days postpartum, aripiprazole was not detectable in colostrum because of an unknown substance that interfered with the assay. On day 27 postpartum, 3 additional milk samples were collected at 30 minutes before the dose (24 hours after the last dose), and 4 and 10 hours after the dose. The drug and its metabolite were undetectable (<10 mcg/L) in all samples. The authors estimated that a fully breastfed infant would receive less than 0.7% of the maternal weight-adjusted dosage.[3]

A woman was taking aripiprazole 18 mg daily. On day 6 postpartum, a breastmilk sample (time not reported) contained a concentration of aripiprazole of 38.7 mcg/L.[4]

A woman took aripiprazole 10 mg daily by mouth beginning in week 9 of pregnancy and continuing postpartum. Mid-nursing milk samples were obtained at 8 and 10 weeks postpartum over a 24-hour period after the dose. Aripiprazole and dehydroaripiprazole were measured in the milk. On the first sampling day, mean milk concentrations were 52.6 mcg/L of aripiprazole and 8.8 mcg/L for the metabolite. On the second day, mean milk concentrations were 53.6 and 6.3 mcg/L, respectively. The authors calculated that a 5 kg infant would receive a daily dose of 47 mcg daily and the weight-adjusted dosage would be 8.3% of the maternal dosage.[5]

Infant Levels. A woman was taking aripiprazole 18 mg daily during pregnancy and postpartum. On day 6 her breastfed infant had a serum concentration of 7.6 mcg/L, although some portion of the concentration could have been residual from transplacental transmission because of the drug's on half-life.[4]

Effects in Breastfed Infants

A woman took aripiprazole 15 mg daily by mouth during pregnancy and postpartum. She breastfed her infant (amount not stated) and at 3 months of age, the infant was growing normally.[3]

A woman took aripiprazole 10 mg daily by mouth beginning in week 9 of pregnancy and continuing postpartum. She exclusively breastfed her infant for 6 weeks, then was partially breastfed. At 4 months of age the infant was still breastfeeding and had normal psychomotor and behavioral development and had reached the expected milestones for her age.[5]

A 12-day-old exclusively breastfed male infant presented with severe weight loss and hypernatremic dehydration because of inadequate milk intake and a 30% weight loss since birth. The infant's mother was being treated for bipolar disorder with lamotrigine 250 mg orally once daily, aripiprazole 15 mg orally once daily, and sertraline 100 mg orally once daily. She was also taking levothyroxine 50 mcg once daily, a prenatal multivitamin, and folic acid. On initial evaluation in the emergency department, he was pale, with marbled skin, dry mucous membranes, decreased skin turgor, and bluish feet with prolonged capillary refill. The right foot eventually became darker with blackened toes and he developed gangrene of the right lower limb, which did not respond to medical therapy and required amputation of all five toes and surgical debridement of the metatarsals. Necrosis was attributed to arterial microthrombi caused by disseminated intravascular coagulation after severe dehydration. The authors considered the mother's medications as a possible cause of the dehydration and related problems.[6]

Effects on Lactation and Breastmilk

Unlike the phenothiazines, aripiprazole has a minimal effect on serum prolactin levels and it has been used to reverse hyperprolactinemia in nonlactating patients taking other antipsychotics.[7][8][9][10][11][12][13][14][15] The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed. However, cases of galactorrhea apparently caused by aripiprazole have been reported.[16][17]

One woman began taking aripiprazole 10 mg daily at week 20 of pregnancy. She underwent a cesarean section delivery at term, but was unable to establish lactation. The authors suggested that more data are needed to determine if aripiprazole adversely affects lactation.[18]

A woman took aripiprazole 10 mg daily by mouth beginning in week 9 of pregnancy and continuing postpartum. She exclusively breastfed her infant for 6 weeks, but then began supplementation because of insufficient milk production. Her serum prolactin was 35 to 40 mcg/L, which is lower than expected for a nursing mother. The authors speculated that the aripiprazole might have been the cause of her low serum prolactin and diminished her milk supply.[5]

A woman with bipolar disorder was taking lithium during pregnancy and postpartum. At 10 days postpartum, her infant's serum lithium level was 0.26 mmol/L, so lithium was discontinued. Quetiapine was begun, but discontinued because of maternal sedation. Aripiprazole 2.5 mg daily was begun and within 24 hours, the mother noted a marked decrease in milk supply. After 2 weeks of working with a lactation consultant, she continued to have lactation difficulties and she switched back to lithium. Within 48 hours, her milk supply improved markedly.[19]

A retrospective study of outpatients receiving an average aripiprazole dose of 17.3 mg daily (n = 20) or another antipsychotic (n = 141) found that those receiving such high-dose aripiprazole had an 81% chance of having hypoprolactinemia. Patients not treated with aripiprazole had only a 2.9% chance of having hypoprolactinemia.[20]

Alternate Drugs to Consider

Haloperidol, Olanzapine, Quetiapine, Risperidone

References

1. Uguz F. Second-generation antipsychotics during the lactation period: A comparative systematic review on infant safety. J Clin Psychopharmacol. 2016;36:244-52. PMID: 27028982

2. Schlotterbeck P, Leube D, Kircher T, Hiemke C, Grunder G. Aripiprazole in human milk. Int J Neuropsychopharmacol. 2007;10:433. PMID: 17291382

3. Lutz UC, Hiemke C, Wiatr G et al. Aripiprazole in pregnancy and lactation a case report. J Clin Psychopharmacol. 2010;30:204-5. Letter. PMID: 20520299

4. Watanabe N, Kasahara M, Sugibayashi R et al. Perinatal use of aripiprazole: a case report. J Clin Psychopharmacol. 2011;31:377-9. PMID: 21532364

5. Nordeng H, Gjerdalen G, Brede WR et al. Transfer of aripiprazole to breast milk: A case report. J Clin Psychopharmacol. 2014;34:272-5. PMID: 24525645

6. Morin C, Chevalier I. Severe hypernatremic dehydration and lower limb gangrene in an infant exposed to lamotrigine, aripiprazole, and sertraline in breast milk. Breastfeed Med. 2017;12:377-80. PMID: 28481632

7. Goodnick PJ, Rodriguez L, Santana O. Antipsychotics: impact on prolactin levels. Expert Opin Pharmacother. 2002;3:1381-91. PMID: 12387684

8. Kane JM, Carson WH, Saha AR et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2002;63:763-71. PMID: 12363115

9. Byerly MJ, Marcus RN, Tran QV et al. Effects of aripiprazole on prolactin levels in subjects with schizophrenia during cross-titration with risperidone or olanzapine: analysis of a randomized, open-label study. Schizophr Res. 2009;107:218-22. PMID: 19038534

10. Boggs AA, Bihday C, Boggs DL. Aripiprazole's effects on risperidone consta induced hyperprolactinemia: A case report. J Pharm Pract. 2012;25:298. Abstract. DOI: doi:10.1177/0897190012441353

11. Lorenz RA, Weinstein B. Resolution of haloperidol-induced hyperprolactinemia with aripiprazole. J Clin Psychopharmacol. 2007;27:524-5. PMID: 17873694

12. Rocha FL, Hara C, Ramos MG. Using aripiprazole to attenuate paliperidone-induced hyperprolactinemia. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:1153-4. PMID: 20547197

13. van Kooten M, Arends J, Cohen D. Preliminary report: a naturalistic study of the effect of aripiprazole addition on risperidone-related hyperprolactinemia in patients treated with risperidone long-acting injection. J Clin Psychopharmacol. 2011;31:126-8. PMID: 21192158

14. Wahl R, Ostroff R. Reversal of symptomatic hyperprolactinemia by aripiprazole. Am J Psychiatry. 2005;162:1542-3. PMID: 16055781

15. Wolf J, Fiedler U. Hyperprolactinemia and amenorrhea associated with olanzapine normalized after addition of aripiprazole. J Clin Pharm Ther. 2007;32:197-8. PMID: 17381670

16. Mendhekar DN, Andrade C. Galactorrhea with aripiprazole. Can J Psychiatry. 2005;50:243. Letter. PMID: 15898468

17. Ruffatti A, Minervini L, Romano M, Sonino N. Galactorrhea with aripiprazole. Psychother Psychosom. 2005;74:391-2. PMID: 16244518

18. Mendhekar D, Sunder KR, Andrade C. Aripiprazole use in a pregnant schizoaffective woman. Bipolar Disord. 2006;8:299-300. PMID: 16696834

19. Frew JR. Psychopharmacology of bipolar I disorder during lactation: a case report of the use of lithium and aripiprazole in a nursing mother. Arch Womens Ment Health. 2015;18:135-6. PMID: 25352315

20. Lozano R, Marin R, Santacruz MJ. Prolactin deficiency by aripiprazole. J Clin Psychopharmacol. 2014;34:539-40. PMID: 24911440

21. Morin C, Chevalier I. Severe hypernatremic dehydration and lower limb gangrene in an infant exposed to lamotrigine, aripiprazole, and sertraline in breast milk. Breastfeed Med. 2017;12:377-80. PMID: 28481632

Important Information

Aripiprazole is not approved for use in psychotic conditions related to dementia. Aripiprazole may increase the risk of death in older adults with dementia-related conditions.

Some young people have thoughts about suicide when taking medicine for a major depressive disorder and other psychiatric disorders. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

What other drugs will affect aripiprazole?

Taking aripiprazole with other drugs that make you sleepy or slow your breathing can cause dangerous or life-threatening side effects. Ask your doctor before taking a sleeping pill, narcotic pain medicine, prescription cough medicine, a muscle relaxer, or medicine for anxiety, depression, or seizures.

Many other drugs can interact with aripiprazole. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with aripiprazole.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2018 Cerner Multum, Inc. Version: 10.05.

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